Progressive Proximal Weakness Research Articles

Clinical Reasoning: A 39-year-old woman with progressive proximal weakness

A 39-year-old woman presented with progressive weakness over the past 2½ years. She initially noticed weakness in her legs after falling while getting out of a boat. Her leg weakness slowly progressed over the next 2 years to the point where she was having great difficulty with stairs and getting up from a sitting position, particularly from low surfaces. In the 2 months prior to her initial visit, she had noticed difficulty reaching overhead. She denied any skin changes, rash, or muscle pain. She did not have any double or blurred vision, ptosis, facial weakness, dysarthria, dysphagia, shortness of breath, numbness, or tingling. Prior to the onset of her symptoms, she had no medical problems apart from asthma and was not taking any medications or supplements. A detailed family history was negative for neurologic disease. Her examination demonstrated mild weakness of the neck flexors (Medical Research Council [MRC] grade 4), and moderate, symmetric, proximal arm and leg weakness (MRC grade 3). Distal muscles were strong. Cognition, cranial nerves, muscle bulk and tone, deep tendon reflexes, sensory examination, and coordination were normal. She had a mild Trendelenburg gait. There was no myotonia or fasciculation. The authors thank Dr. Andrew Engel for providing the images in the figure.

Creatine deficiency syndrome. A treatable myopathy due to arginine–glycine amidinotransferase (AGAT) deficiency

We report two sisters, aged 11 and 6years, with AGAT deficiency syndrome (OMIM 612718) which is the least common creatine deficiency syndrome. They were born full-term to consanguineous parents and had moderate developmental delay. Examination showed an important language delay, a progressive proximal muscular weakness in the lower limbs with Gowers sign and myopathic electromyography. Investigations revealed undetectable guanidinoacetate and low level of creatine in plasma and urine, characteristic findings of AGAT deficiency syndrome. Brain magnetic resonance spectroscopy showed a markedly reduced level of creatine. Guanidinoacetate methyltransferase (GATM) gene sequencing revealed a homozygous missense mutation in exon 4:c.608A>C, (p.Tyr203Ser). Thirteen months after beginning the treatment with oral creatine monohydrate 200mg/kg/day, then 400mg/kg/day, there was a dramatic improvement in muscle strength with Gowers sign disappearance in both patients, and a mild improvement in language and cognitive functions. AGAT deficiency syndrome should be considered in all patients with language retardation and cognitive impairment associated to a myopathy of unknown etiology such that early diagnosis must lead to creatine supplementation to cure the myopathy and improve language and cognitive function.

Association between neurological and rheumatological manifestations in vitamin D deficiency and vitamin D levels

We aimed to investigate the associations between the neurological manifestations of vitamin D deficiency and bone profile as well as the levels of 25-hydroxyvitamin D. We conducted a case series on patients with vitamin D deficiency who were followed up at King Abdulaziz Medical City, Jeddah between January 2010 and December 2011. We collected patients' demographic data and gathered information on etiological factors for vitamin D deficiency as well as clinical presentations (typical, neurological and rheumatological) and radiological findings. The t-test was used to determine whether there was an association between the neurological manifestations of vitamin D deficiency and vitamin D levels and bone profile. We enrolled 60 patients with vitamin D deficiency. Of these, 44 (73.3%) had neurological presentations, namely progressive muscle weakness and proximal weakness, which was observed more often than distal weakness. In addition, gait disturbances were observed in 61.7% of all patients with neurological and rheumatological presentations. There was no significant association between neurological and rheumatological manifestations and bone profile or vitamin D levels. We found a significant association between difficulty in walking and the levels of serum calcium and phosphate (P = 0.043 and 0.037, respectively). Neurological and rheumatologic manifestations of vitamin D deficiency are not associated with 25-hydroxyvitamin D levels or bone profile.

Rapidly progressive asymmetrical weakness in Charcot–Marie–Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy

Charcot-Marie-Tooth disease type 4J (CMT4J), a rare form of demyelinating CMT, caused by recessive mutations in the phosphoinositide phosphatase FIG4 gene, is characterised by progressive proximal and distal weakness and evidence of chronic denervation in both proximal and distal muscles. We describe a patient with a previous diagnosis of CMT1 who presented with a two year history of rapidly progressive weakness in a single limb, resembling an acquired inflammatory neuropathy. Nerve conduction studies showed an asymmetrical demyelinating neuropathy with conduction block and temporal dispersion. FIG4 sequencing identified a compound heterozygous I41T/K278YfsX5 genotype. CMT4J secondary to FIG4 mutations should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy, especially if there is a background history of a more slowly progressive neuropathy.

A case of dry beriberi following bariatric surgery

Case history A 45-year old obese Caucasian lady (155 kg, BMI 57) presented with progressive proximal limb weakness, upper and lower limb paraesthesia, ataxia and athetoid tremors 18 months following a Roux-en-Y gastric bypass surgery. Postoperatively, she had lost 57kg and maintained a healthy diet with moderate alcohol intake (<14 units/week). She admitted non-compl iance wi th mult iv i tamin and Adcal D3 supplementation.

Bethlem myopathy: An autosomal dominant myopathy with flexion contractures, keloids, and follicular hyperkeratosis

Bethlem myopathy and Ullrich congenital muscular dystrophy form a spectrum of collagenopathies caused by genetic mutations encoding for any of the three subunits of collagen VI. Bethlem phenotype is relatively benign and is characterized by proximal dominant myopathy, keloids, contractures, distal hyperextensibility, and follicular hyperkeratosis. Three patients from a single family were diagnosed to have Bethlem myopathy based on European Neuromuscular Centre Bethlem Consortium criteria. Affected father and his both sons had slowly progressive proximal dominant weakness and recurrent falls from the first decade. Both children aged 18 and 20 years were ambulant at presentation. All had flexion contractures, keloids, and follicular hyperkeratosis without muscle hypertrophy. Creatinine kinase was mildly elevated and electromyography revealed myopathic features. Muscle imaging revealed severe involvement of glutei and vasti with “central shadow” in rectus femoris. Muscle biopsy in the father showed dystrophic changes with normal immmunostaining for collagen VI, sarcoglycans, and dysferlin.

A Late-Onset Case of Neutral Lipid Storage Disease with Myopathy,Dropped Head Syndrome, and Peripheral Nerve Involvement

Neutral lipid storage disease with myopathy (NLSDM) is a rare autosomal recessive disorder of neutral lipid metabolism. Clinical manifestations include progressive skeletal myopathy, cardiomyopathy, and liver dysfunction. Clinical severity is variable and additional symptoms may include diabetes mellitus, chronic pancreatitis, hypothyroidism, neurosensory hearing loss, and short stature. We report a 79-year-old man with progressive proximal arm weakness, lipid storage myopathy, dropped head syndrome, and peripheral nervous system involvement. He harboured a novel homozygous missense mutation, c.570A>C (p.S191R) in the patatin-like phospholipase domain containing 2 (PNPLA2) gene, confirming the diagnosis of NLSDM. The S191R mutation causes late-onset NLSDM without cardiac dysfunction. The previously unreported association with dropped head syndrome expands the clinical spectrum of NLSDM.

Maximizing Functional Independence in Sporadic Late Onset Nemaline Myopathy

Sporadic late onset nemaline myopathy (SLONM) is a rare neuromuscular disorder of unknown pathogenesis. The incidence of nemaline myopathy is estimated to be 1:500,000 [1]; however, the late onset subtype accounts for only 4% of cases [2]. Nemaline rods, the characteristic feature of nemaline myopathy, arise from the z band of the sarcomere and are composed primarily of -actinin [1]. However, nemaline bodies may be present in a variety of conditions, including human immunodeficiency virus (HIV) infection, mitochondrial myopathy, and central core disease [1]. In SLONM, the diagnosis is based on characteristic findings of progressive proximal weakness, normal creatine kinase, myopathic motor unit (short duration, low amplitude) and fibrillation potentials on electromyography (EMG), and a muscle biopsy that demonstrates nemaline rods [3]. SLONM is associated with monoclonal gammopathy of undetermined significance (MGUS) [3]. The presence of a monoclonal gammopathy confers a high risk of mortality; 57% of individuals with this disease are reported to die of respiratory failure within 2 years of onset of muscle weakness. Alternatively, patients with SLONM and without a monoclonal gammopathy did not die of their disease when followed-up 4-23 years after symptom onset. Therefore, patients with SLONM may survive for many years, likely with functional impairment secondary to muscle weakness. To our knowledge, the rehabilitation process has never been described for a patient with SLONM. We theorize that structured rehabilitation therapy is an important component in maximizing functional ability for patients with SLONM.

Les myopathies nécrosantes acquises

Necrotizing myopathies (MN) are defined by a specific histological pattern. They are characterized by a predominant muscle fibre necrosis and regeneration but with little or no associated inflammation. This histological pattern is observed in acquired myopathy but also in muscular dystrophy. Acquired NM can be secondary to drugs or toxics, and if not, autoimmune mechanisms have to be suspected. Necrotizing autoimmune myopathy is recognized as a subgroup of idiopathic inflammatory myopathies, different from other myositides. Generally, patients present a rapidly progressive and severe symmetrical proximal weakness with high serum creatine kinase level, associated in some patients with cardiac involvement. On the other hand, a slower progression may sometimes be observed, that could lead to erroneous diagnosis of muscular dystrophy. Necrotizing autoimmune myopathy may be associated to specific autoantibodies against signal recognition particle, or more recently described, against 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Necrotizing auto-immune myopathy can also be described in association with connective tissue diseases such as lupus or sclerodermia. In remaining cases, cancer association may be observed. Necrotizing autoimmune myopathies are now considered as a new entity, treatable by immunosuppressants and which should not be misdiagnosed as a muscular dystrophy.

G.P.32 Progressive core myopathy with dilated cardiomyopathy, respiratory failure and severe scoliosis caused by a novel mutation in the MYH7 gene

Heterozygous mutations in the MYH7 gene, encoding for the slow/beta-cardiac myosin heavy chain, are responsible for a wide spectrum of myopathies variably affecting cardiac or skeletal muscle, such as hypertrophic cardiomyopathy, Laing distal myopathy (MPD1), congenital fibre type disproportion, scapuloperoneal myopathy and myosin storage myopathy. Occurrence of both skeletal myopathy and cardiomyopathy has so far been described only in a few families. Here we report about a family with a novel MYH7 mutation, presenting with a progressive phenotype affecting both skeletal and cardiac muscles. The index case, aged 28years at time of last assessment, showed first symptoms at 1year of age. The phenotype was characterized by progressive proximal and distal weakness, severe scoliosis requiring spinal fixation at 9years of age, joint contractures and significant involvement of neck flexors and extensors. The patient lost ambulation at the age of 16years and subsequently developed respiratory insufficiency, dilated cardiomyopathy and seizures. His daughter showed first symptoms at the age of 3years, with mild proximal weakness, tiredness, joint hypermobility and a progressive scoliosis. CK values were normal and muscle biopsy showed type 1 fibre atrophy in both patients. The index case also showed feature of a core myopathy in his biopsy. Analysis of the MYH7 gene identified a heterozygous c.4823G>C (p.Arg1608Pro) variant in exon 34. Interestingly the unaffected father of the index case was mosaic for the c.4823G>C mutation. The degree of somatic mosaicism was not assessed and no other family members were found to carry the MYH7 variant. Missense mutations to proline disrupting the ability of the myosin tail to form a coiled coil are known to cause MPD1. Our findings expand the severe end of the phenotypic spectrum of conditions associated with MYH7 mutations.

D.P.22 Muscle ultrasound as a consistent imaging marker for RYR1 related myopathies

Skeletal muscle ultrasound applications in neuromuscular medicine are increasing since high frequency transducers are capable of generating images of much improved resolution. Similar to MRI, diagnostic ultrasound imaging phenotypes are being identified, such as the finding of a “central cloud” in the rectus femoris of patients with collagen six myopathy. Here we describe an ultrasound imaging phenotype that is characteristic for RYR1 related myopathies: sparing of the rectus femoris next to a significantly increased echogenicity in the vastus lateralis. RYR1 related myopathies include the histological phenotypes of central core disease, multi-minicore disease, centro-nuclear myopathy. In addition to these established histological phenotypes muscle biopsy findings may be non-specific with a myopathic or dystrophic appearance and the presence of significant fibroadipose tissue. Clinically, autosomal dominant forms more commonly present with static or slowly progressive proximal weakness involving hip and axial muscles but can also be severe in infancy. Recessive forms typically present with more severe early hypotonia and weakness, and with extraocular muscle involvement in a number of patients. This clinical and histopathological variability can give rise to diagnostic confusion and delay. Muscle MRI has been shown to demonstrate relative sparing of the rectus femoris in patients with RYR1 mutations, but the acquisition of such an imaging study often requires sedation in this younger patient population that may also be at risk for malignant hyperthermia. Muscle ultrasound can demonstrate the same imaging phenotype via a quick, painless and highly tolerable bedside procedure. Here we present 15 patients with genetically proven RYR1 related myopathies with a variety of clinical, histological and genetic findings all demonstrating a consistent an ultrasound imaging phenotype. This easily obtained imaging finding may thus help to guide diagnostic considerations.

G.P.80 Non-sense mutation in exon two of the dystrophin gene results in mild Becker muscular dystrophy with generalized muscle hypertrophy

Becker muscular dystrophy leads to progressive proximal weakness. Focal wasting is commonly seen in the calves, less typically in other locations such as the thenar eminence. Generalized muscle hypertrophy has been described with other muscular dystrophies such as LGMD 1A and in a X-linked myopathy with postural muscle atrophy caused by mutation in the FHL gene. Generalized muscle hypertrophy with Becker muscular dystrophy (BMD) has not been reported before. We present a patient with muscle pain from adolescence. On examination he had generalized muscle hypertrophy, but preserved muscle strength and a 10- to 20-fold elevated CPK. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. MRI showed a normal distribution between muscle and fat confirming that his large body volume was caused by generalized muscle hypertrophy. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with generalized muscle hypertrophy. The unusual clinical presentation suggests that the phenotype is caused by a translation re-initiation downstream for the mutation site.

Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2

Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest that this unusual phenotype is caused by translation re-initiation downstream from the mutation site.

A 61-year-old man presented with myopathy, neuropathy, and inflammatory dermatitis responsive to chronic lymphocytic leukemia treatment

The prevalence of paraneoplastic neurologic syndrome in cancer is 0.01%. Neurological syndromes can be seen in chronic lymphocytic leukemia (CLL) and mostly present as either leukemic infiltration of the central nervous system (CNS) or progressive multifocal leukoencephalopathy. To our knowledge, this is the first reported case of combined sensory-motor neuropathy, myopathy, and dermatitis in a patient with CLL.Case presentationA 61-year-old African American man presented with acute dysphagia, rapidly progressive proximal limb-girdle weakness, and dermatitis. He had a white blood cell (WBC) count of 14,600/mm3, hemoglobin of 11.4 mg/dL, and a platelet count of 165,000/mm3. Lymphocytes comprised 15% of the total WBC with an absolute lymphocyte count of 2100/mm3. Metabolic profile was unremarkable except for a serum creatine phosphokinase (CPK) level of 1056 mg/dL. Serum protein electrophoresis, serologic studies for autoimmune, genetic diseases, and paraneoplastic syndromes were all negative. Electrodiagnostic studies revealed sensorimotor neuropathy with mixed axonal and demyelinating features. Muscle biopsy revealed discrete areas of interstitial fibrosis juxtaposed to areas of intact muscle without any inflammation. At that point, a bone marrow biopsy was done because of anemia and slightly elevated mean corpuscular volume of 103. Bone marrow biopsy revealed minimal involvement with CD5/CD19-positive CLL. Flow cytometry demonstrated monoclonal CD5/CD19/CD20/CD23-positive cells, with dim kappa expression, and negative FMC-7 and CD3. This case doesn’t meet the criteria for CLL/small lymphocytic lymphoma. However, considering the possibility of paraneoplastic phenomenon for his symptoms, it was decided to start the patient on CLL-directed therapy with Rituximab and Cyclophosphamide. After only two cycles, the patient experienced a dramatic improvement in his muscle strength with disappearance of the rash.ConclusionThis case highlights a unique clinical picture of inflammatory dermatitis with electromyography and biopsy findings suggestive of myopathy and combined sensorimotor neuropathy with response to CLL-directed therapy. Also the symptoms started before peripheral lymphocytosis which masked the diagnosis for over a year.

A case of necrotizing myopathy with proximal weakness and cardiomyopathy

A male amateur body builder presented at age 23 years with a 2-year history indicative of progressive proximal limb weakness. His initial symptom was a rash which was nonpruritic and he described as “ring” lesions on his trunk which spontaneously resolved after 6 months. Following resolution of

Expanding the Spectrum of ANO5-Muscular Dystrophy: Skeletal Muscle Amyloidosis, Cardiac Arrhythmia and Novel Mutations (PD6.001)

Objective: To investigate the clinical and pathological spectrum of ANO5-muscular dystrophy. Background Anoctamin-5 (ANO5) is a putative calcium-activated chloride channel and is highly expressed in skeletal and cardiac muscles and in bone. Dominant mutations in ANO5 cause gnathodiaphyseal dysplasia, while recessive mutations result in limb-girdle muscular dystrophy or distal myopathy. Design/Methods: Clinical examination, EMG, EKG, echocardiography, muscle histochemical studies, and mutational analysis in 4 unrelated patients. Results:Patient (Pt) 1: A 53-year-old woman with exercise-induced myalgia since childhood, rhabdomyolysis, adult-onset progressive limb-girdle weakness and asymmetric calf atrophy and weakness. Pt2: A 42-year-old man with progressive asymmetric distal and proximal weakness and paroxysmal atrial fibrillation since late 309s. Pt3: A 32-year-old woman with delayed motor milestones, myalgia, progressive limb-girdle weakness since mid 209s, and supraventricular tachyarrhythmia requiring ablation. Pt 4: A 68-year-old man with long standing history of asymptomatic hyper-CKemia followed by weakness of the calf muscles, subsequently extending to the limb-girdle muscles. All patients had elevated CK and myopathic EMG changes. Muscle biopsy revealed nonspecific myopathic changes in Pt1, Pt2, and Pt4; signs of reinnervation in Pt3; and amyloid deposits within the interstitium and blood vessel walls in Pt1 and Pt2. Echocardiogram revealed septal wall global hypokinesis in Pt3 and normal findings in the other patients. All 4 patients harbored two heterozygous ANO5 mutations; Pt2, Pt3 and Pt4 carry novel ANO5 mutations. Conclusions: The presence of cardiac arrhythmia in 2/4 patients suggest that cardiac involvement can occur in ANO5-muscular dystrophy and underlines the need for close cardiac monitoring. The presence of skeletal muscle amyloidosis in 2/4 patients increases the pathological similarity between ANO5-muscular dystrophy and dysferlinopathy and provides a clue to the diagnosis in the absence of dysferlin deficiency and/or dysferlin mutations. Supported by: The Neurology Department at Mayo Clinic, Rochester MN. Disclosure: Dr. Liewluck has nothing to disclose. Dr. Dimberg has nothing to disclose. Dr. Winder has received personal compensation for activities with PreventionGenetics. Dr. Milone has nothing to disclose.

Findings and treatment of a rare case presentation of painful neuroborreliosis

The painful component of Neuroborreliosis is potentially a severe and debilitating complication of Lyme disease and is thoroughly underreported in pain literature. Case reports of successful treatment of pain component are also not well described. We describe a rare case of painful Neuroborreliosis successfully treated with neuropathic agent gabapentin. A 68 y male in usual health with 4 weeks history of progressive torso numbness, paresthesias, back pain, and proximal leg weakness. Six weeks prior to admission, noted acute episode of interscapular back pain after golfing in CT, progressive to flanks, groin and lower extremities bilaterally. No documentation of tick bite. PO opioid rotation unsuccessful. Rapid progressive weakness to lower extremity paraplegia upon presentation to hospital. Full diagnostic work-up: positive confirmatory serum IgM and IgG Lyme Ab by Western Blot. Patient diagnosed with Neuroborreliosis; discharged home with 3 weeks IV ceftriaxone with full neurological resolution, however with remanent pain symptoms. Patient presents to Pain Center three weeks post discharge. Intense pins/needles sensation in T8-T12 dermatomal distribution with significant hyperhydrosis on affected dermatomes. Physical exam demonstrates thoracolumbar neuropathy secondary to recent history of Lyme disease with inflammatory radiculopathy. Given neuropathic model of pain, patient prescribed gabapentin. Within three weeks of escalating doses of gabapentin, patient's painful radiculitis completely resolved with total of 300mg BID dose. There is unclear mechanism of effects of Lyme disease on the nervous system, and particularly on dorsal column neurons. While case reports of neurologic sequelae of Lyme disease is plentiful in neurological literature, the painful syndromes and neuropathies that result are far more rare, and probably unknown to the pain physician. The use of gabapentin, even low dose, in this case shows very impressive result in treating painful Neuroborreliosis. (Halperin JJ. Curr Treat Options Neurol 2007.)

Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy

How to Cite this Article: Karimzadeh P, Ghazavi A. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy. IranianJournal of Child Neurology 2012;6(1):5-12. Objective Duchenne muscular dystrophy (DMD) is a degenerative disease that usually becomes clinically detectable in childhood as progressive proximal weakness. No cure is yet available for DMD, but the use of steroids improves muscle strength and function. This study has been carried out to select the best steroid for the management of DMD. Materials & Methods This study is a single-blind, randomized clinical trial with a sample volume of 34 DMD patients. Half of these patients were treated with deflazacort (0.9 mg/kg daily) and the other half with prednisone (0.75 mg/kg daily) for a period of 18 months. The motor function score and excess body weight were registered one year after the start and also at the end of the study and compared between the two groups. Results Deflazacort was more effective in the improvement of motor function after one year, but there was no significant difference between the two drugs at the end of the study (18 months after start). Weight gain after one year and at the end of the study was higher in prednisone group and steroid treatment with deflazacort appears to cause fewer side effects than prednisone regarding weight gain. Conclusion Deflazacort seems to be more effective than prednisone in the improvement of motor function causing fewer side effects, particularly weight gain. This medication may be important for the improvement of motor function and could be used as the best steroidal treatment for Duchenne muscular dystrophy. References Lankester BJA, Whitehouse MR, Gargan MF. Duchenne muscular dystrophy. Current Orthopedics 2007;21:298- 300. Wenger DR, Rang M. The art and practice of children’s orthopedics. Philadelphia, PA: Lippincott; Baltimore: Williams and Wilkins; 1993. Sussman M. Duchenne muscular dystrophy. J Am Acad Orthop Surg 2002 Mar-Apr;10(2):138-51. Escolar DM, Leshner RT. Muscular dystrophies. In: Swaiman KF, Ashwal S, Ferriero DM. Pediatric Neurology. 4th ed. Philadelphia: Mosby; 2006. p. 1967-86. Sarnat HB, Menkes JH. Disease of the motor unit. In: Menkes JH, Sarnat HB, editors. Child Neurology. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 984-9. Biggar WD, Politano L, Harris VA, Passamano L, Vajsar J, Alman B, et al. Deflazacort in duchenne muscular dystrophy: a comparison of two different protocols. Neuromuscul disord 2004 Sep;14(8-9):476-82. Radley HG, De Luca A, Lynch GS, Grounds MD. Duchenne muscular dystrophy: focus on pharmaceutical and nutritional interventions. Int J Biochem Cell Biol 2007;39(3):469-77. Biggar WD, Klamut HJ, Demacio PC, Stevens DJ. Duchenne muscular dystrophy: current knowledge, treatment and future prospects. Clin Orthop Relat Res 2002 Aug;401:88-106. Sohn RL, Gussoni E. Stem cell therapy for muscular dystrophy. Expert Opin Biol Ther 2004 Jan;4(1):1-9. Houde S, Filiatrault M, Fournier A, Dube J, D’Arcy S, Berube D et al. Deflazacort use in duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol 2008 Mar;38(3):200-6. Bonifati MD, Ruzza G, Bonometto P, Berardinelli A, Gorni K, Orcesi K et al. A multicenter double-bind randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy: analysis after 2 years. Basic Appl Myol 2000;10:171-5. Reitter B. Deflazacort vs. prednisone in Duchenne muscular dystrophy: trends of an ongoing study. Brain Dev 1995;17 Suppl:39-43. Polgar G, Promadhat V. Standard values. In: pulmonary function testing in children: techniques and standards. Philadelphia: W.B. Saunders, 1971:102-3. Biggar WD, Gingras M, Febling DL, Harris VA, Steele CA. Deflazacort treatment of Duchenne muscular dystrophy. J Pediatr 2001 Jan;138(1):45-50.

A Case of Lambert-Eaton Myasthenic Syndrome with Small-Cell Lung Cancer and Transient Increase in Anti-Acetylcholine-Receptor-Binding Antibody Titer

BackgroundLambert-Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder that is most frequently associated with small-cell lung cancer (SCLC). The titers of antibodies against voltage-gated calcium channels are frequently increased in LEMS, but only rarely is titer of anti-acetylcholine-receptor-binding antibodies (AChR-abs) increased.Case ReportA 57-year-old male was admitted to our hospital due to dry mouth and eyes and progressive proximal limb weakness of 2 months duration. The results of a repetitive nerve stimulation test disclosed all criteria for the electrophysiological LEMS pattern, and the patient's AChR-abs titer was 0.587 nmol/L. At a follow-up performed 5 years after successful treatment of SCLC and LEMS, his AChR-abs titer had decreased to 0.001 nmol/L.ConclusionsWe suggest that this was a case of transient pseudopositivity of AChR-abs in SCLC with LEMS.

A case of acute sarcoid myositis treated with weekly low-dose methotrexate

A 25-year-old man was referred to our hospital with a 2-month history of progressive proximal extremity weakness. His serum creatine kinase (CK) level was extremely elevated, and chest X-ray revealed bilateral hilar lymphadenopathy and small nodules in bilateral lung fields. Biopsy specimens obtained from muscle and lung revealed non-caseating epithelioid cell granulomas. On the basis of these findings, the patient was diagnosed with sarcoidosis and acute sarcoid myositis. Although steroid pulse therapy was administered repeatedly, the muscle symptoms did not improve, and the serum CK level remained high. We added 7.5 mg oral methotrexate once per week to oral prednisolone, and this improved both the muscle weakness and the CK level. Concurrent administration of methotrexate could be a therapeutic option for cases with acute sarcoid myositis refractory to steroid therapy.