3. Pareyson D, Marchesi C. Diagnosis, natural history and management of Charcot-Marie-Tooth disease. Lancet Neurol 2009;7:654–667. 4. Matthews E, Fialho D, Tan SV, Venance SL, Cannon SC, Sternberg D, et al. The non-dystrophic myotonia: molecular pathogenesis, diagnosis and treatment. Brain 2010;133:9–22. 5. Lehmann-Horn F, Jurkat-Rott K and R€ udel R. Diagnostics and therapy of muscle channelopathies—guidelines of the Ulm Muscle Centre. Acta Myol 2008;XXVII:98—113. 6. Brugnoni R, Kapetis D, Imbrici P, Pessia M, Canioni E, Colleoni L, et al. A large cohort of myotonia congenita probands: novel mutations and a high-frequency mutation region in exons 4 and 5 of the CLCN1 gene. J Hum Genet 2013;58:581–587. 7. Leiden Open Variation Database. Chloride channel 1, skeletal muscle (CLCN1). http://chromium.liacs.nl/LOVD2/; 2012. 8. Aarskog NK, Vedeler CA. Real-time quantitative polymerase chain reaction. A new method that detects both the perypheral myelin protein 22 duplication in Charcot–Marie–Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary neuropathy with liability to pressure palsies. Hum Genet 2000;107:494–498. 9. Kim HS, Chung KW, Kang SH, Choi SK, Cho SY, Koo H, et al. Myotonic dystrophy type I combined with X-linked dominant Charcot– Marie–Tooth neuropathy. Neurogenetics 2010;11:425–433. 10. Kurt S, Karner H, Kaplan Y, Akat I, Battaloglu E, Druslu D, et al. Combination of myotonic dystrophy and hereditary motor and sensory neuropathy. J Neurol Sci 2010;288:197–199. 11. Bergman C, Senderek J, Hermanns B, Jauch A, Janssen B, Schroder JM, et al. Becker muscular dystrophy combined with Xlinked Charcot–Marie–Tooth neuropathy. Muscle Nerve 2000;23: 818–823. 12. Schreiber O, Schneiderat P, Kress W, Rautenstrauss B, Senderek J, Schoser B, et al. Facioscapulohumeral muscular dystrophy and Charcot–Marie–Tooth neuropathy 1A—evidence for “double-trouble” overlapping syndromes. BMC Med Genet 2013;14:92. 13. Hodapp JA, Carter GT, Lipe HP, Michelson SJ, Kraft GH, Bird TD. Double trouble in hereditary neuropathy: concomitant mutations in the PMP-22 gene and another gene produce novel phenotypes. Arch Neurol 2006;63:112–117.
Published online 11 February 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24205
---------------------------------------------------------
MYOPATHY RELATED TO VITAMIN D DEFICIENCY IN PATIENT WITH CELIAC DISEASE Myopathy has a wide variety of etiologies, including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness, metabolic, and other systemic disorders.1 Celiac disease is a leading consideration in patients with the malabsorption syndrome and atypical manifestations such as anemia, osteoporosis, vitamin D malabsorption, and myopathy.2,3 We describe a patient with celiac disease and myopathy due to severe vitamin D deficiency, which was confirmed by electrophysiological findings. A 17-year-old woman presented with proximal muscle weakness in both upper and lower extremities for a few months. She had a 5-year history of celiac disease, which was diagnosed during investigation of anemia. Her family history was unremarkable. On neurological examination, bilateral proximal muscle strength of upper extremities was 4/5, and proximal muscle strength of lower extremities was 3/5. The remainder of the neurological examination was normal, including sensory and reflex testing.
The white-cell and platelet counts, liver function tests, albumin, and thyroid stimulating hormone were within the normal range. The hemoglobin level was 11.2 g/dL (reference range, 12–15.5 g/dl), but creatine kinase (CK) was 210 lg/L (reference range, 10–120 lg/ L). An autoimmune work-up (anti-nuclear, rheumatoid factor, and Anti-Jo-1 antibodies) was negative. Other laboratory findings included: ferritin, 14 ng/ml (reference range, 18–160 ng/ml), vitamin B12, 204 pg/ml (reference range, 200–900 pg/ml), vitamin D (25-hydroxyvitamin D), < 4 ng/dl (reference range, 30–80 ng/dl), calcium 8.5 mg/dl (reference range, 8.8–10.5 mg/dl), and phosphorus, 3.6 mg/dl (reference range, 2.4–4.1 mg/dl). Anti-endomysial immunoglobulin A (IgA) was negative, anti-tissue transglutaminase and anti-gliadin IgA antibodies were positive. Endoscopic biopsy from the duodenum showed damage to the villi. On electrophysiological examination, sensory and motor conduction studies were normal. The results of needle electromyography are listed in Table 1. Because of no history or laboratory-clinical manifestation of metabolic, medication, alcohol, or drug-induced myopathy, no findings of systemic disease or rhabdomyolysis, the patient was diagnosed with myopathy due to severe vitamin D deficiency related to celiac disease. A gluten-free diet with vitamin D3 supplementation (300,000 U/per 2 weeks) was started. Myopathic symptoms resolved within 1 week, and after 3 weeks of treatment, the CK level returned to normal levels. The patient was in good condition and displayed no signs of celiac disease on endoscopic examination after 6 months followup. Due to the elimination of other etiologies and a dramatic response of myopathic symptoms to vitamin D treatment, muscle biopsy was not performed. Vitamin D deficiency can occur in patients with celiac disease because of both low intake and poor absorption. The exact pathophysiology underlying myopathy due to vitamin D deficiency is still unclear, but musculoskeletal disorders and myopathy associated with very low serum vitamin D levels are well defined in the literature.4 Besides the effect of vitamin D on bone and mineral metabolism, it also has anti-proliferative, pro-differentiation, immunomodulatory, and anti-inflammatory functions by binding to the vitamin D receptor.5 These roles may also have a protective effect in myopathies. Vitamin D deficiency should be considered in patients with acquired myopathy of unknown cause. Ozgur Zeliha Karaahmet, MD1 Ece Unlu, MD,2 Fatih Karaahmet, MD3 Eda Gurcay, MD2 Aytul Cakci, MD1 1
Department of Physical Medicine & Rehabilitation, Ministry of Health Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey
2
Department of Physical Medicine & Rehabilitation, Ministry of Health Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey
Correspondence to: F. Karaahmet, e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Letters to the Editor
3
Department of Gastroenterology, Ministry of Health Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey MUSCLE & NERVE
July 2014
147
Table 1. Needle EMG findings.* Spontaneous activity
R. deltoid R.vastus medialis R. iliopsoas R. biceps R. first dorsal interosseos R. tibialis anterior
MUP
Recruitment
IA
fib
PSW
fasc
H.F
amp
dur
poly
pattern
N N N N N N
None None None None None None
11 21 21 None None None
None None None None None None
None None None None None None
N N N N N N
N N N N N N
11 11 21 N N N
N N 11 N N N
*MUP, motor unit potential; IA, insertional activity; fib, fibrillation potentials; PSW, positive sharp waves; HF, high frequency discharges; dur, duration; poly, polyphasia; R, right. 1. Jackson CE, Barohn RJ. A pattern recognition approach to myopathy. Continuum (Minneap Minn). 2013;19(6 Muscle Disease):1674–1697. 2. Selva-O’Callaghan A, Casellas F, de Torres I, Palou E, Grau-Junyent JM, Vilardell-Tarr es M. Celiac disease and antibodies associated with celiac disease in patients with inflammatory myopathy. Muscle Nerve 2007;35:49–54. 3. Hadjivassiliou M, Chattopadhyay AK, Gr€ unewald RA, Jarratt JA, Kandler RH, Rao DG, et al. Myopathy associated with gluten sensitivity. Muscle Nerve 2007;35:443–450. 4. Shinchuk LM, Holick MF. Vitamin D and rehabilitation: improving functional outcomes. Nutr Clin Pract 2007; 22:297–304. € Yuksel I, Coban S, Yuksel O. Vitamin D sup5. Karaahmet F, Basar O, plementation and the irritable bowel syndrome. Aliment Pharmacol Ther 2013;37:499.
Published online 23 February 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24217
FIGURE 1. Analysis of the EMG recording using different settings (A–E). Calibration is same for (D) and (E).
--------------------------------------------------------MOTOR UNIT POTENTIAL INDUCED NEUROTONIA (MINT) We have read with interest the description of the “motor unit potential (MUP) induced iterative discharge (MIRD)”, by So and colleagues.1 We have also seen similar signals in patients with neuropathy. However, we have interpreted this iterative discharge (ID) as a form of neurotonia.2 One recording made in the deltoid muscle of a patient with cervical radiculopathy is shown in Figure 1. The ID occurred intermittently, but only following an MUP discharge. The firing rate within the ID was roughly 100 HZ. The signals were high pass filtered (1000 HZ) for jitter analysis.3 The triggered sweeps are shown in a superimposed fashion in Figure 1B. Spikes 1–5 belonged to the MUP, whereas spikes 6–9 belonged to the ID. Only the first cycle of the ID is shown. Spike 5 from the MUP was used for triggering. The jitter in the ID spikes was normal and was >5 ls (upper limit for ephaptic transmission; Fig. 1F), hence this ID cannot be considered to be a complex repetitive discharge (CRD). However, due to the low normal jitter and high discharge rate, the signal had a “mechanical” sound similar to a CRD.
The MUP is unstable by visual assessment. Note that spikes 1 and 2 move together on successive discharges (Fig. 1C). Spikes 3 and 4 show a similar pattern. Jitter (Fig. 1F) is normal between spikes 1 and 2 and also between spikes 3 and 4. However, the jitter is very high between spikes 2 and 3, and there is no blocking. This pattern of “neurogenic jitter”3 indicates a defect in excitability and conduction in the terminal axon branch. Nerve conduction variability is also seen as distinct positions of the spikes. The 2 positions for the ID seen in Figure 1B have been described as “flip-flop”.3 In Figure 1D, spike 2 has 4 different positions. When traces with ID are separated (Fig. 1E), the ID occurs only when spike 2 is in the leftmost position (Fig. 1D and E, vertical dotted line). We conclude that abnormal conduction and excitability in a terminal axon branch caused the ID and MUP variability. Because only a part of the MU (distal to the defective terminal branch) was involved in the ID, the repeating potential is smaller than the MUP. Combined with the high firing rate (100 HZ), we characterized this ID as a “MUP-induced neurotonia (MINT)”,4 or a “partial multiplet”. Sanjeev D. Nandedkar, PhD1 Paul E. Barkhaus, MD2 1
Natus Medical, Inc., Middleton, Wisconsin, USA
2
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Additional Supporting Information may be found in the online version of this article. C 2014 Wiley Periodicals, Inc. V
148
Letters to the Editor
1. So NF, Rubin DI, Jones LK, Litchy WJ, Sorenson EJ. Motor unit potential induced repetitive discharges (MIRDs): description of an unusual iterative discharge. Muscle Nerve 2013;48:977–979. 2. Barkhaus PE, Nandedkar SD. Electronic atlas of EMG waveforms. Hopewell Junction, NY: Nandedkar Productions; 2007.
MUSCLE & NERVE
July 2014
Published online 11 February 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24205
---------------------------------------------------------
MYOPATHY RELATED TO VITAMIN D DEFICIENCY IN PATIENT WITH CELIAC DISEASE Myopathy has a wide variety of etiologies, including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness, metabolic, and other systemic disorders.1 Celiac disease is a leading consideration in patients with the malabsorption syndrome and atypical manifestations such as anemia, osteoporosis, vitamin D malabsorption, and myopathy.2,3 We describe a patient with celiac disease and myopathy due to severe vitamin D deficiency, which was confirmed by electrophysiological findings. A 17-year-old woman presented with proximal muscle weakness in both upper and lower extremities for a few months. She had a 5-year history of celiac disease, which was diagnosed during investigation of anemia. Her family history was unremarkable. On neurological examination, bilateral proximal muscle strength of upper extremities was 4/5, and proximal muscle strength of lower extremities was 3/5. The remainder of the neurological examination was normal, including sensory and reflex testing.
The white-cell and platelet counts, liver function tests, albumin, and thyroid stimulating hormone were within the normal range. The hemoglobin level was 11.2 g/dL (reference range, 12–15.5 g/dl), but creatine kinase (CK) was 210 lg/L (reference range, 10–120 lg/ L). An autoimmune work-up (anti-nuclear, rheumatoid factor, and Anti-Jo-1 antibodies) was negative. Other laboratory findings included: ferritin, 14 ng/ml (reference range, 18–160 ng/ml), vitamin B12, 204 pg/ml (reference range, 200–900 pg/ml), vitamin D (25-hydroxyvitamin D), < 4 ng/dl (reference range, 30–80 ng/dl), calcium 8.5 mg/dl (reference range, 8.8–10.5 mg/dl), and phosphorus, 3.6 mg/dl (reference range, 2.4–4.1 mg/dl). Anti-endomysial immunoglobulin A (IgA) was negative, anti-tissue transglutaminase and anti-gliadin IgA antibodies were positive. Endoscopic biopsy from the duodenum showed damage to the villi. On electrophysiological examination, sensory and motor conduction studies were normal. The results of needle electromyography are listed in Table 1. Because of no history or laboratory-clinical manifestation of metabolic, medication, alcohol, or drug-induced myopathy, no findings of systemic disease or rhabdomyolysis, the patient was diagnosed with myopathy due to severe vitamin D deficiency related to celiac disease. A gluten-free diet with vitamin D3 supplementation (300,000 U/per 2 weeks) was started. Myopathic symptoms resolved within 1 week, and after 3 weeks of treatment, the CK level returned to normal levels. The patient was in good condition and displayed no signs of celiac disease on endoscopic examination after 6 months followup. Due to the elimination of other etiologies and a dramatic response of myopathic symptoms to vitamin D treatment, muscle biopsy was not performed. Vitamin D deficiency can occur in patients with celiac disease because of both low intake and poor absorption. The exact pathophysiology underlying myopathy due to vitamin D deficiency is still unclear, but musculoskeletal disorders and myopathy associated with very low serum vitamin D levels are well defined in the literature.4 Besides the effect of vitamin D on bone and mineral metabolism, it also has anti-proliferative, pro-differentiation, immunomodulatory, and anti-inflammatory functions by binding to the vitamin D receptor.5 These roles may also have a protective effect in myopathies. Vitamin D deficiency should be considered in patients with acquired myopathy of unknown cause. Ozgur Zeliha Karaahmet, MD1 Ece Unlu, MD,2 Fatih Karaahmet, MD3 Eda Gurcay, MD2 Aytul Cakci, MD1 1
Department of Physical Medicine & Rehabilitation, Ministry of Health Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey
2
Department of Physical Medicine & Rehabilitation, Ministry of Health Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey
Correspondence to: F. Karaahmet, e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Letters to the Editor
3
Department of Gastroenterology, Ministry of Health Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey MUSCLE & NERVE
July 2014
147
Table 1. Needle EMG findings.* Spontaneous activity
R. deltoid R.vastus medialis R. iliopsoas R. biceps R. first dorsal interosseos R. tibialis anterior
MUP
Recruitment
IA
fib
PSW
fasc
H.F
amp
dur
poly
pattern
N N N N N N
None None None None None None
11 21 21 None None None
None None None None None None
None None None None None None
N N N N N N
N N N N N N
11 11 21 N N N
N N 11 N N N
*MUP, motor unit potential; IA, insertional activity; fib, fibrillation potentials; PSW, positive sharp waves; HF, high frequency discharges; dur, duration; poly, polyphasia; R, right. 1. Jackson CE, Barohn RJ. A pattern recognition approach to myopathy. Continuum (Minneap Minn). 2013;19(6 Muscle Disease):1674–1697. 2. Selva-O’Callaghan A, Casellas F, de Torres I, Palou E, Grau-Junyent JM, Vilardell-Tarr es M. Celiac disease and antibodies associated with celiac disease in patients with inflammatory myopathy. Muscle Nerve 2007;35:49–54. 3. Hadjivassiliou M, Chattopadhyay AK, Gr€ unewald RA, Jarratt JA, Kandler RH, Rao DG, et al. Myopathy associated with gluten sensitivity. Muscle Nerve 2007;35:443–450. 4. Shinchuk LM, Holick MF. Vitamin D and rehabilitation: improving functional outcomes. Nutr Clin Pract 2007; 22:297–304. € Yuksel I, Coban S, Yuksel O. Vitamin D sup5. Karaahmet F, Basar O, plementation and the irritable bowel syndrome. Aliment Pharmacol Ther 2013;37:499.
Published online 23 February 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mus.24217
FIGURE 1. Analysis of the EMG recording using different settings (A–E). Calibration is same for (D) and (E).
--------------------------------------------------------MOTOR UNIT POTENTIAL INDUCED NEUROTONIA (MINT) We have read with interest the description of the “motor unit potential (MUP) induced iterative discharge (MIRD)”, by So and colleagues.1 We have also seen similar signals in patients with neuropathy. However, we have interpreted this iterative discharge (ID) as a form of neurotonia.2 One recording made in the deltoid muscle of a patient with cervical radiculopathy is shown in Figure 1. The ID occurred intermittently, but only following an MUP discharge. The firing rate within the ID was roughly 100 HZ. The signals were high pass filtered (1000 HZ) for jitter analysis.3 The triggered sweeps are shown in a superimposed fashion in Figure 1B. Spikes 1–5 belonged to the MUP, whereas spikes 6–9 belonged to the ID. Only the first cycle of the ID is shown. Spike 5 from the MUP was used for triggering. The jitter in the ID spikes was normal and was >5 ls (upper limit for ephaptic transmission; Fig. 1F), hence this ID cannot be considered to be a complex repetitive discharge (CRD). However, due to the low normal jitter and high discharge rate, the signal had a “mechanical” sound similar to a CRD.
The MUP is unstable by visual assessment. Note that spikes 1 and 2 move together on successive discharges (Fig. 1C). Spikes 3 and 4 show a similar pattern. Jitter (Fig. 1F) is normal between spikes 1 and 2 and also between spikes 3 and 4. However, the jitter is very high between spikes 2 and 3, and there is no blocking. This pattern of “neurogenic jitter”3 indicates a defect in excitability and conduction in the terminal axon branch. Nerve conduction variability is also seen as distinct positions of the spikes. The 2 positions for the ID seen in Figure 1B have been described as “flip-flop”.3 In Figure 1D, spike 2 has 4 different positions. When traces with ID are separated (Fig. 1E), the ID occurs only when spike 2 is in the leftmost position (Fig. 1D and E, vertical dotted line). We conclude that abnormal conduction and excitability in a terminal axon branch caused the ID and MUP variability. Because only a part of the MU (distal to the defective terminal branch) was involved in the ID, the repeating potential is smaller than the MUP. Combined with the high firing rate (100 HZ), we characterized this ID as a “MUP-induced neurotonia (MINT)”,4 or a “partial multiplet”. Sanjeev D. Nandedkar, PhD1 Paul E. Barkhaus, MD2 1
Natus Medical, Inc., Middleton, Wisconsin, USA
2
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Additional Supporting Information may be found in the online version of this article. C 2014 Wiley Periodicals, Inc. V
148
Letters to the Editor
1. So NF, Rubin DI, Jones LK, Litchy WJ, Sorenson EJ. Motor unit potential induced repetitive discharges (MIRDs): description of an unusual iterative discharge. Muscle Nerve 2013;48:977–979. 2. Barkhaus PE, Nandedkar SD. Electronic atlas of EMG waveforms. Hopewell Junction, NY: Nandedkar Productions; 2007.
MUSCLE & NERVE
July 2014
