Muscle ultrasound elastography and MRI in preschool children with Duchenne muscular dystrophy

The aim of this study was to determine muscle tissue elasticity, measured with shear-wave elastography, in selected lower limb muscles of patients affected by Duchenne muscular dystrophy (DMD) and to correlate the values obtained with those recorded in healthy children and with muscle magnetic resonance imaging (MRI) data from the same DMD children, specifically the pattern on T1-weighted (w) and short-tau inversion recovery (STIR) sequences. Five preschool DMD children and five age-matched healthy children were studied with shear-wave elastography. In the DMD children, muscle stiffness was moderately higher compared with the muscle stiffness in HC, in the rectus femoris, vastus lateralis, adductor magnus and gluteus maximus muscles. On muscle MRI T1-w images showed fatty replacement in 3/5 patients at the level of the GM, while thigh and leg muscles were affected in 2/5; hyperintensity on STIR images was identified in 4/5 patients. No significant correlation was observed between stiffness values and MRI scoring. Our study demonstrated that lower limb muscles of preschool DMD patients show fatty replacement and patchy edema on muscle MRI and increased stiffness on shear-wave elastography. In conclusion, although further studies in larger cohorts are needed, shear-wave elastography could be considered a useful non-invasive tool to easily monitor muscle changes in early stages of the disease.     

Asymmetrical patchy muscle involvement in manifesting carriers of Duchenne muscular dystrophy--computed tomographical and histological study

Two cases of manifesting carriers of Duchenne muscular dystrophy (DMD) were described. Case 1. The 41 year-old woman presented gait disturbance at the age of 40. She had two sons. The first son died of pneumonia soon after birth. The second son developed DMD and died of heart failure when he was 17 years old. Neurological examination revealed mild muscle weakness in neck flexors, gluteus maximus (left side dominance) and hamstrings (right side dominance) as well as bilateral calf pseudohypertrophy. Electromyography showed myopathic changes and serum creatine kinase (CK) was elevated (1941IU/l). The karyotype was 46XX. Computed tomography (CT) of skeletal muscles showed that the following muscles were partly replaced by fatty tissue: bilateral paravertebral muscles, left gluteus maximus, left quadriceps femoris, right adductor magnus, long head of right biceps femoris, bilateral peroneus longus and medial head of left gastrocnemius. Histological examination of left quadriceps femoris revealed only minimal change of focal endomysial proliferation and fiber size variation, demonstrating no necrotic fiber or no abnormalities in fiber type. Case 2. The 42 year-old woman was admitted to the hospital complaining of dyspnea and palpitation. The disease was initially diagnosed as myocardial infarction based on cardiomegaly, ECG abnormality (Q in aVL, V5,6., ST depression and negative T in V5,6, ST elevation in I, aVL) and elevated serum CK. However, the diagnosis was rejected due to the lack of subsequent changes in ECG and the continued elevation of serum CK even after her complaints had disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnetic resonance imaging in duchenne muscular dystrophy: Longitudinal assessment of natural history over 18 months

Introduction: In Duchenne muscular dystrophy (DMD), fat replacement of muscle may be a useful endpoint in trials of therapy, although progression in different muscle groups is uneven. In this study we assessed the progression of fat replacement with T₁‐weighted imaging over 2 9‐month periods. Methods: Eight ambulant, corticosteroid‐treated boys with DMD were imaged at 3 Tesla at 3 time‐points (baseline and 9 and 18 months) with T₁‐weighted imaging to measure fat replacement. Results: The greatest increase in fat content was measured in the biceps femoris long head, vastus lateralis, and rectus femoris, whereas the biceps femoris short head and gluteus maximus progressed more slowly. None of the lower leg muscles studied changed significantly. Conclusions: MRI can measure specific changes in fat replacement of muscle over time, demonstrating the variability in rates of natural progression between muscle groups and identifying those muscles suitable for use as biomarkers in clinical trials. Muscle Nerve 48 : 586–588, 2013     

Proton spin-lattice relaxation time of Duchenne dystrophy skeletal muscle by magnetic resonance imaging

By means of proton MRI, the spin-lattice relaxation times (T1 values) of pelvic and leg muscles were measured in Duchenne muscular dystrophy (DMD) patients and normal controls. The bound water fraction (BWF) was calculated from the T1 value obtained. In normal children, the T1 value decreased, and BWF increased with age. In DMD, the T1 value rapidly decreased, from an abnormally high value in the early stages, with the progress of the disease. This reduction of the T1 value in DMD was not the same for all muscles; it was most prominent in the gluteus maximus and least prominent in the sartorius and gracilis muscles. BWF was below normal in the early stages of DMD. It is suggested that both regenerating and degenerating muscle fibers, together with the increased muscle water content, cause the high T1 value and low BWF in the early stages of DMD, whereas replacement of muscle by fat causes the decreased T1 value in the advanced stages.     

Muscle imaging findings in GNE myopathy

GNE myopathy (MIM 600737) is an autosomal recessive muscle disease caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Besides the typical phenotype, characterized by the initial involvement of the distal leg muscles that eventually spreads proximally with sparing of the quadriceps, uncommon presentations with a non-canonical clinical phenotype, unusual muscle biopsy findings or both are increasingly recognized. The aim of our study was to characterize the imaging pattern of pelvic and lower limb muscles in GNE myopathy, thus providing additional diagnostic clues useful in the identification of patients with atypical features. We retrospectively evaluated muscle MRI and CT scans of a cohort of 13 patients heterogeneous for GNE mutations and degree of clinical severity. We found that severe involvement of the biceps femoris short head and, to a lesser extent, of the gluteus minimus, tibialis anterior, extensor hallucis and digitorum longus, soleus and gastrocnemius medialis was consistently present even in patients with early or atypical disease. The vastus lateralis, not the entire quadriceps, was the only muscle spared in advanced stages, while the rectus femoris, vastus intermedius and medialis showed variable signs of fatty replacement. Younger patients showed hyperintensities on T2-weighted sequences in muscles with a normal or, more often, abnormal T1-weighted signal. Our results define a pattern of muscle involvement that appears peculiar to GNE myopathy. Although these findings need to be further validated in a larger cohort, we believe that the recognition of this pattern may be instrumental in the initial clinical assessment of patients with possible GNE myopathy.     

Muscle magnetic resonance imaging in patients with LAMA2-related muscular dystrophy

LAMA2-related muscular dystrophy (LAMA2-MD) is classified into congenital muscular dystrophy type 1A (MDC1A) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23). The purpose of this study was to identify the involvement pattern of thigh muscles of LAMA2-MD patients on magnetic resonance imaging. Fourteen MDC1A and 3 LGMDR23 patients were included, with 21 known and 8 novel LAMA2 disease-causing variants. In LAMA2-MD, the gluteus maximus, anterior (quadriceps femoris) and posterior (adductor magnus and biceps femoris) thigh muscles were extensively and severely affected with fatty infiltration, with relatively sparing of the adductor longus. The pattern of muscle involvement was similar between MDC1A and LGMDR23, but more severe in MDC1A, as well as in LAMA2-MD patients without ambulation. The rather peculiar pattern of the adductor magnus and long head of the biceps femoris first and severely affected in the mid-thigh level was found in LGMDR23. Strong correlation between fatty infiltration and age as well as disease duration was observed for the adductor longus in MDC1A. Edema and atrophy selectively involved in some muscles. The pattern of fatty infiltration on thigh muscle MRI of LAMA2-MD could provide important information for the diagnosis, differential diagnosis and assessment of clinical severity.     

Distinct neuromuscular phenotypes in myotonic dystrophy types 1 and 2

Myotonic Dystrophy Type 1 (DM1) and 2 (DM2) present with distinct though overlapping clinical phenotypes. Comparative imaging data on skeletal muscle involvement are not at present available. We used the novel technique of whole body 3.0 Tesla (T) Magnetic Resonance Imaging (MRI) to further characterize musculoskeletal features in DM2 and compared the results with DM1. MRI findings of 15 DM1 and 14 DM2 patients were evaluated with respect to patterns of skeletal muscle affection and clinical data using the Muscular Impairment Rating Scale (MIRS) and Medical Research Council scale (MRC). All DM1 patients had pathological MRI compared with only 5 DM2 patients. In contrast to DM2, DM1 patients showed a characteristic distribution of muscle involvement with frequent and early degeneration of the medial heads of gastrocnemius muscles, and a perifemoral semilunar pattern of quadriceps muscle affection sparing the rectus femoris. The most frequently affected muscles in DM1 were the medial heads of gastrocnemius, soleus, and vastus medialis muscles. In DM2, however, the erector spinae and gluteus maximus muscles were most vulnerable to degeneration. MRI data were in line with the clinical grading in 12 DM1 and 3 DM2 patients. In 3 DM1 and 5 DM2 patients, MRI detected subclinical muscle involvement. 9 DM2 patients with mild to moderate proximal muscle weakness and/or myalgias had normal MRI. Pathological MRI changes in DM2 emerged with increasing age and were restricted to women. Whole body 3.0T MRI is a sensitive imaging technique that demonstrated a characteristic skeletal muscle affection in DM1. In contrast, MRI was no reliable indicator for skeletal muscle involvement in mildly affected DM2 patients since myalgia and mild paresis were usually not reflected by MRI signal alterations.     

A method for positioning electrodes during surface EMG recordings in lower limb muscles

PURPOSE: The aim of this work is to provide information about the degree of inter-subject uniformity of location of innervation zone (IZ) in 13 superficial muscles of the lower limb. The availability of such information will allow researchers to standardize and optimize their electrode positioning procedure and to obtain accurate and repeatable estimates of surface electromyography (sEMG) signal amplitude, spectral variables and muscle fiber conduction velocity. METHODS: Surface EMG signals from gluteus maximus, gluteus medius, tensor faciae latae, biceps femoris, semitendinosus, vastus medialis obliquus, vastus lateralis, rectus femoris, tibialis anterior, peroneus longus, soleus, gastrocnemius medialis and lateralis muscles of ten healthy male subjects aged between 25 and 34 years (average = 29.2 years, S.D. = 2.5 years) were recorded to assess individual IZ location and signal quality. RESULTS: Tensor faciae latae, biceps femoris, semitendinosus, vastus lateralis, gastrocnemius medialis and lateralis showed a high level of both signal quality and IZ location uniformity. In contrast, rectus femoris, gluteus medius and peroneus longus were found to show poor results for both indexes. Gluteus maximus, vastus medialis obliquus and tibialis anterior were found to show high signal quality but low IZ location uniformity. Finally, soleus muscle was found to show low signal quality but high IZ location uniformity. CONCLUSIONS: This study identifies optimal electrode sites for muscles in the lower extremity by providing a standard landmarking technique for the localization of the IZ of each muscle so that surface EMG electrodes can be properly positioned between the IZ and a tendon.     

Rimmed vacuolar distal myopathy: a clinical,electrophysiological, histopathological and computed tomographic study of seven cases

Summary The following report describes the clinical, laboratory, electrophysiological, histopathological and computed tomographic studies of seven cases of distal myopathy with rimmed vacuoles in the muscle fibers. Each displayed several characteristic features. First, the onset was in early adulthood. Second, there was a unique distribution of muscle involvement: tibialis anterior and extensor digitorum and hallucis muscles were initially and most severely affected. The hamstrings and adductors of the thigh were also markedly involved. The gluteus medius and minimus muscles and the neck flexors were mildly affected in the relatively early stages. In contrast, the gastrocnemius, soleus, quadriceps femoris, and gluteus maximus muscles were well preserved until an advanced stage. Third, serum creatine kinase activity was normal or only mildly elevated; fourth, EMG were mainly myopathic, with certain neuropathic features; and fifth, histopathologically rimmed vacuoles in muscle fibers were found associated with certain neuropathic features, such as angular fibers, clustering of atrophic fibers, pyknotic nuclear clumps, and fiber-type predominance. The characteristic distribution of skeletal muscle involvement was particularly noticeable, together with certain neuropathic features of the EMG and muscle biopsy in rimmed vacuolar distal myopathy.     

Musculi longus capitis et splenius der Ratte und innervierende Motoneurone

Summary The nuclei for the nerves of a dorsal (m. splenius) and a ventral (m. longus capitis) neck muscle of the rat were retrogradely labeled by applying horseradish peroxidase (HRP) to the respective cut muscle nerves. Motoneurons of both muscles were analyzed for their localization, diameter of perikarya, and area of dendritic arborization. The nucleus of m. longus capitis is situated dorsomedially, the nucleus of m. splenius ventromedially within the ventral horn. Thus, the relative positions of the two nuclei are inverse to those of their muscles, with the more ventral nucleus innervating the more dorsal muscle.In both nuclei the areas of dendritic arborization are very large, extending into the nuclei of other neck muscles, and also into the ipsilateral anterior funiculus. In addition, m. longus capitis motoneurons were found to send dendrites into the contralateral ventral horn, reaching the nucleus of the contralateral muscle.The size distribution of perikarya is bimodal for m. longus capitis motoneurons, but only unimodal in the case of m. splenius.

Diese Arbeit wurde teilweise durch die Hartmann-Müller-Stiftung unterstützt     

Nociceptive pathway function is normal in cervical dystonia: a study using laser-evoked potentials

Cervical dystonia (CD) is often associated with pain in the neck muscles, though the mechanisms underlying pain in this condition are still largely unknown. The aim of this study was to assess laser pain rating and CO(2) laser-evoked potentials (LEPs) in CD patients with pain in the posterior neck region. We assessed the N2/P2 LEP complex and laser pain rating in a group of 20 CD patients and in 21 normal subjects. In 11 of the 20 CD patients (group I), the N2/P2 complex was recorded after stimulation of the skin overlying the right and left deltoid muscles (painless and non-dystonic). In the remaining nine CD patients (group II), the N2/P2 complex was recorded after stimulation of the skin over the splenius capitis muscle (painful and dystonic) and after stimulation of the skin overlying the contralateral splenius muscle (painless and non-dystonic). In group I patients, the N2/P2 LEP amplitude and laser pain rating after stimulation of both shoulders did not differ significantly from those obtained in normal subjects. Similarly, in group II patients, the N2/P2 LEP amplitude and laser pain rating after stimulation of the painful and dystonic splenius capitis muscle did not differ significantly from those obtained from either the contralateral painless, non-dystonic splenius capitis or normal subjects. The results of this study demonstrate that cutaneous nociceptive pathway function in CD patients is normal, thereby indicating that muscle pain in CD is not associated with any central sensitization of nociceptive inputs in either painful (dystonic) or non-painful (non-dystonic) body areas.     

Whole-body muscle MRI characteristics of LAMA2-related congenital muscular dystrophy children: An emerging pattern

Merosin-deficient or LAMA2-related congenital muscular dystrophy (CMD) belongs to a group of muscle diseases with an overlapping diagnostic spectrum. MRI plays an important role in the diagnosis and disease-tracking of muscle diseases. Whole-body MRI is ideal for describing patterns of muscle involvement. We intended to analyze the pattern of muscle involvement in merosin-deficient CMD children employing whole-body muscle MRI. Ten children with merosin-deficient CMD underwent whole-body muscle MRI. Eight of which were genetically-confirmed. We used a control group of other hereditary muscle diseases, which included 13 children (mean age was 13 SD +/- 5.5 years), (8 boys and 5 girls) for comparative analysis. Overall, 37 muscles were graded for fatty infiltration using Mercuri scale modified by Fischer et al. The results showed a fairly consistent pattern of muscle fatty infiltration in index group, which differs from that in control group. There was a statistically significant difference between the two groups in regard to the fatty infiltration of the neck, serratus anterior, intercostal, rotator cuff, deltoid, triceps, forearm, gluteus maximus, gluteus medius, gastrocnemius and soleus muscles. Additionally, the results showed relative sparing of the brachialis, biceps brachii, gracilis, sartorius, semitendinosus and extensor muscles of the ankle in index group, and specific texture abnormalities in other muscles. There is evidence to suggest that whole-body muscle MRI can become a useful contributor to the differential diagnosis of children with merosin deficient CMD. The presence of a fairly characteristic pattern of involvement was demonstrated. MRI findings should be interpreted in view of the clinical and molecular context to improve diagnostic accuracy.     

Segmental distribution of muscle weakness in SMA III: implications for deterioration in muscle strength with time

We examined 26 spinal muscular atrophy type III (SMA III) patients with SMNt deletions, searching for possible segmental distribution of muscle weakness. In those with disease duration of ≤11 years, the weakest muscles were upper lumbar innervated ones in the lower extremities. In the upper extremities, early involvement of triceps muscle suggested the possibility of lower cervical (C7) onset. Electrophysiologically, weaker muscles had a more severe reduction in the recruitment pattern, particularly in the lower extremities. However, severe reduction in recruitment was sometimes also observed in clinically strong muscles. In patients with disease duration of ≥16 years and regardless of disease duration, in those with disease onset at ≤3 years of age, weakness and severe electrophysiological changes were more widespread. These findings may suggest a progression in muscle weakness with time. When compared to 12 patients with Becker muscular dystrophy (BMD), early stage SMA III with weak iliopsoas-strong gluteus maximus stood in contrast to BMD with weak gluteus maximus-strong iliopsoas.     

A case of distal myopathy with rimmed vacuole formation, progresses into proximal-dominant muscle involvement]

A case of 55-year-old male with distal myopathy with rimmed vacuole formation is reported. He first noticed dragging of his legs at the age of forty-three. Two years later, he was evaluated to have muscle wasting and weakness in lower legs. In another ten years, he became unable to stand or walk unaided. On physical examination, proximal limb muscles were more severely affected than distal limb muscles. Notably, muscle strength of the quadriceps femoris muscles were weak (MRC Scale 3/5), compared to hamstrings, tibialis anterior muscle and gastrocnemius muscle (4/5). Serum creatine kinase, electromyography, nerve conduction velocities were all compatible with this diagnosis. A computed tomography of the musculoskeletal system was consistent with physical findings. Muscle biopsy revealed many fibers with typical rimmed vacuoles (approximately 6% of fibers). Additionally, small amount of ragged-red fibers (0.5%) was noted. Histochemical reaction showed a focal deficiency of cytochrome c oxidase. This case suggests that during the longstanding course of the illness, proximal limb muscles may be more severely affected, and quadriceps femoris muscle may be predominantly involved.     

MRC sum-score in the ICU: good reliability does not necessarily reflect "true reliability"

Introduction: Muscle and cardiac metabolism are dependent on the oxidation of fats and glucose for adenosine triphosphate production, for which L ‐carnitine is an essential cofactor. Methods: We measured muscle carnitine concentrations in skeletal muscles, diaphragm, and ventricles of C57BL/10ScSn‐DMDmdx/J mice (n = 10) and compared them with wild‐type C57BL/6J (n = 3), C57BL/10 (n = 10), and C3H (n = 12) mice. Citrate synthase (CS) activity was measured in quadriceps/gluteals and ventricles of mdx and wild‐type mice. Results: We found significantly lower tissue carnitine in quadriceps/gluteus (P < 0.05) and ventricle (P < 0.05), but not diaphragm of mdx mice, when compared with controls. CS activity was increased in mdx quadriceps/gluteus (P < 0.03) and ventricle (P < 0.02). This suggests compensatory mitochondrial biogenesis. Conclusions: Decreased tissue carnitine has implications for reduced fatty acid and glucose oxidation in mdx quadriceps/gluteus and ventricle. The mdx mouse may be a useful model for studying the role of muscle carnitine deficiency in DMD bioenergetic insufficiency and providing a targeted and timed rationale for L ‐carnitine therapy. Muscle Nerve 46: 767–772, 2012     

Age-related conversion of dystrophin-negative to -positive fiber segments of skeletal but not cardiac muscle fibers in heterozygote mdx mice

Immunoreactive dystrophin was examined in muscle fibers of quadriceps, extraocular muscles and cardiac ventricular muscles of female heterozygote mdx mice at 10, 35 and 60 days of age, with microscopic immunoperoxidase method and by immunoblots. In quadriceps muscle fibers there was a marked gradual diminution of the dystrophin-negative fiber segments between age 10 and 60 days. We suggest that this was partly due to a spontaneous fusion of dystrophin-competent satellite cells into the dystrophin-negative fiber segments and partly to an expansion of the cytoplasmic domain of dystrophin expression related to the original myonuclei. In cardiac muscle that lacks satellite cells, there was persistence of a large number of dystrophin-negative fiber segments even at age 60 days and probably beyond. The findings of this study have implications for the detection of heterozygote female carriers of Duchenne muscular dystrophy (DMD) and for the possible therapy of DMD muscles by myoblast transfer.     

Terminal sprouting of mouse motor nerves when the post-synaptic membrane degenerates

Injection of ecothiopate, 4-aminopyridine and caffeine into the mouse calf produced necrosis in the endplate region of approximately 40% of soleus muscle fibres. Within two days terminal sprouting, as seen by zinc iodide/osmium tetroxide staining, had occurred at nearly a quarter of such endplates, but not at neighbouring intact ones. Almost half of these sprouts were greater than 50 μm in length. Terminal sprouting at degenerating endplates was also seen in identically treated silver-stained gluteus maximus muscles. Muscle degeneration caused by mechanical damage produced similar effects. In transverse sections of the gluteus maximus preparation, the terminals could be found within the necrotic muscle fibres, having penetrated the synaptic basal lamina. It is concluded that motor nerve terminals have an intrinsic tendency to grow, and are normally prevented from doing so by their formation of synapses with muscle fibres. Destruction of this relationship alone can cause terminal sprouting.     

Clinical and pathological studies on two patients with adult-onset nemaline myopathy

Clinical and pathological findings of two patients, a 44-year-old male and a 54-year-old female, with adult-onset nemaline myopathy were described. Both patients showed normal motor development through their childhood; Patient 1 ran fast and was involved in powerful heavy labor until the age of 40, and Patient 2 was in good health until 49, when they began to have progressive muscle weakness. They had no family history of neuromuscular diseases. On neurological examination, they had moderate muscle weakness and atrophy in their limb-girdle and paravertebral muscles. Because paravertebral and neck muscles were preferentially involved, they had difficulty in holding the head straight up. They stood in a lordotic posture. They had neither high-arched palate nor facio-skeletal abnormalities which were common findings in congenital nemaline myopathy. Serum enzymes derived from muscle were normal and needle electromyography showed myogenic and neurogenic changes in both patients. On CT scan of the skeletal muscles, the paravertebral muscles were markedly decreased in density suggesting advanced fat tissue replacement in large areas. In patient 2 who was in more advanced stage, the quadriceps femoris, hamstrings and soleus muscles also showed the similar CT findings. Light microscopic examination of biopsied biceps brachii (Patient 1) and quadriceps femoris (Patient 2) demonstrated abundant rod-like structures in the majority of type 1 fibers. In both patients, there was a marked variation in fiber size. Type 1 fibers were atrophic and type 2C fibers increased in number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical progression in Charcot–Marie-Tooth disease type 1A duplication: clinico-electrophysiological and MRI longitudinal study of a family

Long-term follow-up studies in Charcot–Marie-Tooth disease type 1 duplication (CMT1A) are scanty. Here we describe a longitudinal study in a CMT1A pedigree. Our CMT1A pedigree comprised 11 examined patients, ages between 13 and 83 (median, 36) years, serially evaluated for up to 26 years. In all 11 patients we carried out electrophysiological evaluation, and in three of them magnetic resonance imaging (MRI) of lower-limb musculature. The 54-year-old proband patient, yearly examined as of age 28, developed at age 48 gradual and progressive distal lower-leg weakness ascending to thigh musculature. His serial electrophysiological studies showed diffuse slowing of motor conduction velocity, absence or severe attenuation of distal compound muscle action potentials, and spontaneous muscle activity in the tibialis anterior and rectus femoris. Two MRI studies of lower limbs, at ages 51 and 54, showed extensive fatty atrophy of lower-leg musculature, and progressive and distally accentuated fatty atrophy of anterior and posterior femoral muscles. An outstanding finding in the first MRI was the presence of marked edema of anterior femoral musculature, which to a great degree was replaced by fatty atrophy in the second study. Muscle edema was also noted in lower-leg and posterior femoral musculature. There was minimal fatty atrophy of the gluteus maximus, the remaining pelvic muscles being preserved. The other ten patients showed mild or moderate phenotype, which remained quiescent over the period of observation. Electrophysiological studies disclosed diffuse and uniform slowing of nerve conduction velocities; in no case was spontaneous muscle activity recorded. MRI showed the CMT1A characteristic pattern of distally accentuated fatty atrophy involving foot and lower-leg musculature with preservation of thigh musculature. We conclude that a small proportion of patients with CMT1A develop a late progression of disease manifested with accentuated distal leg weakness ascending to involve thigh musculature, and that long-term follow-up is essential for its detection.