Online newspaper of professor Yasser Metwally

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

March 9, 2010 — NF1 is the most common of the phakomatoses, occurring in approximately 1 in 3500 individuals worldwide. Its manifestations may also be the most wide ranging. The hallmark pathologic lesion is the neurofibroma, a benign tumor of the nerve sheath [3]. Neurofibromas may occur anywhere in the body, either as focal nodules or encompassing multiple nerve fascicles (plexiform neurofibroma). Focal neurofibromas occur in the skin, where they can cause major disfigurement, or internally, where they can lead to nerve compression or invade the spinal canal. For the most part, focal neurofibromas are not present in young children but begin to appear in the preadolescent years and then unpredictably throughout life. Puberty and pregnancy are times when neurofibromas commonly appear or grow, suggesting a hormonal influence [4]. Plexiform neurofibromas, in contrast, tend to be congenital and often grow during the early years of life, sometimes causing soft tissue enlargement leading to hypertrophy [5]. Plexiform neurofibromas can be deeply rooted and hence difficult to remove surgically. Plexiform neurofibromas may cause major cosmetic disfigurement or functional impairment. (Click to download a case record in PDF format…557 KB)

Figure 1. Multiple cutaneous neurofibromas (Click to magnify figure)

NF1 is an unpredictable and protean disorder [6,7]. The presenting sign is usually the occurrence of multiple café-au-lait macules, noticed in the early months of life [8]. Six or more such spots larger than 5 mm before puberty or larger than 15 mm after puberty constitutes a diagnostic criterion [9]. Skin-fold freckles appearing between 3 and 5 years of age constitutes a second criterion. Other diagnostic criteria are the occurrence of iris Lisch nodules (melanocytic hamartomas), which are commonly present in adults with NF1; optic glioma; characteristic skeletal dysplasia (orbital or tibial dysplasia); two or more neurofibromas or one plexiform neurofibroma; and an affected first-degree relative. The presence of two or more features establishes the clinical diagnosis of NF1, but diagnosis often requires observation over a period of time, because many of the features are age dependent. Genetic testing is becoming available and is discussed later.

Figure 2. Lisch nodules (Click to magnify figure)

Management of NF1 is currently limited to surveillance for treatable complications, anticipatory guidance, and genetic counseling. Treatment consists mostly of surgical removal of symptomatic neurofibromas. Dermal tumors can be removed by plastic surgery or other techniques, such as CO2 laser [10] or electrodessication. It is usually impossible to resect plexiform neurofibromas fully, but judicious debulking can be helpful. Recurrence tends to be correlated with degree of resection [11]. Children with tibial bowing can be managed with bracing to avoid the risk of fracture [12]. Learning disabilities and attention deficit disorder are common and respond to standard interventions [13].

Life expectancy in NF1 is reduced on average, although many experience a normal lifespan [14]. Mortality associated with the disorder is usually caused by malignancy or vascular problems. The risk of NF-associated malignancy is estimated at 10% [15]. The major tumor type is malignant peripheral nerve sheath tumor, usually arising from a plexiform neurofibroma. These tumors present clinically with sudden growth or pain, usually in the second through fourth decades. Although there may be imaging signs suggesting malignancy, such as hemorrhage or cystic components [16], the diagnosis is often difficult because an affected individual is likely to have multiple benign tumors. Increased metabolic activity detected by positron emission tomography scanning may help distinguish benign from malignant lesions [17]. Other nonneural malignancies that are increased in frequency in NF1 include leukemia, particularly juvenile myelomonocytic leukemia, and rhabdomyosarcoma [18].

NF1 is also associated with an increased risk of glioma. The most common lesion is the optic glioma [19]. Evidence of optic glioma can be recognized by imaging in approximately 15% of children with NF1, typically before 6 years of age [20,21]. Tumors can occur in the orbit, the chiasm, or both, and can be unilateral or bilateral. Associated symptoms include proptosis, pain, visual impairment, constricted visual fields, or neuroendocrine disturbance (for chiasmatic tumors). Neuroendocrine disturbance most often takes the form of precocious puberty. Optic gliomas are commonly asymptomatic, in spite of progression visualized by imaging, and growth may be self limiting. As a consequence, treatment is reserved for those with progressive symptomatic lesions. Radiation therapy has been all but abandoned in young children with optic gliomas because of the high risk of vascular dysplasias, malignancies, and cognitive deficits. Chemotherapy with vincristine and carboplatinum is now used as a first-line therapy for those with symptomatic optic glioma [22].

Figure 3. Left optic nerve glioma with thickening of the nerve and proptosis, Unidentified bright object (UBO) within the brain parenchyma, Radial and ulnar bowing and obliteration of the intramedullary spaces. (Click to magnify figure)

Because optic gliomas often do not require therapy, there has been controversy regarding whether asymptomatic children with NF1 should be screened by brain MR imaging. Proponents note that such screening identifies children at greater risk and allows for close follow-up [23]. Others argue that asymptomatic lesions will not be treated, so it is more efficient to monitor first for signs and symptoms, offering imaging to those with a suspicion of harboring an active lesion [24].

Gliomas can occur elsewhere in the brain or spinal cord. Most often these (like optic gliomas) are pilocytic astrocytomas, and most are relatively slow growing. Gliomas in individuals with NF1 tend to be more indolent in their progression than their counterparts in non–NF1-affected individuals. Gliomas need to be distinguished from areas of enhanced T2 signal intensity seen by MR imaging, which are common in children with NF1 and tend to disappear with time [25,26]. These NF spots are not space occupying and do not cause distinct neurologic signs. The overall number of such spots may correlate with the occurrence of learning disabilities, however [27–30].

Nontumor manifestations of NF1 may contribute significantly to morbidity. Skeletal dysplasia, most often involving long bones, especially the tibia, can lead to fracture and pseudoarthrosis [12]. This dysplasia is a congenital problem, so a child found not to have tibial bowing is not at risk. Approximately 50% of children with NF1 have learning disabilities [31]. There is no NF-specific pattern, and there may be associated attention deficit disorder and neuromotor developmental delays. Early recognition of learning disabilities is important to implement customized educational plans.

NF1 is an autosomal dominant disorder with complete penetrance and a high rate of new mutation. An affected individual has a 50% risk of transmitting the disorder to any offspring, with no way to predict severity. Approximately 50% of cases arise from a new mutation, in which case both parents are free of clinical signs. Somatic mosaicism may present as segmental NF, in which the features are confined to a restricted region of the body, or as mild NF [32,33]. Germline mosaicism has been reported [34], which means that recurrence risk for an unaffected couple is slightly higher than the general population risk.

The gene for NF1 resides on chromosome 17 and encodes a protein referred to as neurofibromin [35]. Neurofibromin includes a guanosine triphosphate (GTPase)-activating protein domain that regulates the conversion of Ras-GTP to Ras-GDP, thereby exerting an effect to control signal transduction within the cell [36]. The NF1 gene functions as a tumor suppressor, so that mutation of both alleles is required to unleash tumor growth. Affected individuals are heterozygous, leading to a high frequency of tumors caused by somatic mutation of the wild-type allele. It is not clear whether nontumor manifestations, such as learning disabilities, also occur because of a tumor suppressor mechanism or whether these result from haploinsufficiency of NF1 function in heterozygous cells.

The discovery of the NF1 gene has shed light on the pathogenesis of the disorder and is beginning to affect clinical management. Genetic testing for purposes of diagnosis, including prenatal diagnosis, is now possible [37]. The gene is large, and mutations are widely scattered along the gene, so a multitiered approach has been most successful. Clinical trials are beginning, using drugs that may impact the function of the Ras pathway and other drugs such as angiogenesis inhibitors [38]. Clinical trials for NF1 are listed by the National Neurofibromatosis Foundation at www.nf.org/clinical_trials . One of the major targets of treatment has been the plexiform neurofibroma. Volumetric MR imaging may provide a means of measuring the rate of change in the size of these large and irregular lesions [39].

References

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3. Korf B. Neurofibromas and malignant tumors of the peripheral nervous system. In: Friedman JM, Gutmann DH, MacCollin M, Riccardi VM, eds. Neurofibromatosis: phenotype, natural history, and pathogenesis. Baltimore: Johns Hopkins 1999:142-161
4. Dugoff L, Sujansky E. Neurofibromatosis type 1 and pregnancy. Am J Med Genet. 1996;66:7-10
5. Korf BR. Plexiform neurofibromas. Am J Med Genet. 1999;89(1):31-37
6. Carey JC, Laub JM, Hall BD. Penetrance and variability in neurofibromatosis: a genetic study of 60 families. Birth Defects: Orig Artic Ser. 1979;15(5B):271-281
7. Huson SM, Harper PS, Compston DAS. Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales. Brain. 1988;111:1355-1381
8. Korf BR. Diagnostic outcome in children with multiple cafe au lait spots. Pediatrics. 1992;90(6):924-927
9. Stumpf DA, Alksne JF, Annegers JF, Brown SS, Conneally PM, Housman D, et al. Neurofibromataosis. Arch Neurol. 1988;45:575-578
10. Moreno JC, Mathoret C, Lantieri L, Zeller J, Revuz J, Wolkenstein P. Carbon dioxide laser for removal of multiple cutaneous neurofibromas. Br J Dermatol. 2001;144(5):1096-1098
11. Needle MN, Cnaan A, Dattilo J, Chatten J, Phillips PC, Shochat S, et al. Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974–1994. J Pediatr. 1997;131(5):678-682
12. Crawford AH, Schorry EK. Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg. 1999;7(4):217-230
13. North KN, Riccardi V, Samango-Sprouse C, Ferner R, Moore B, Legius E, et al. Cognitive function and academic performance in neurofibromatosis 1: consensus statement from the NF1 cognitive disorders task force. Neurology. 1997;48(4):1121-1127
14. Rasmussen SA, Yang Q, Friedman J. Mortality in neurofibromatosis 1: an analysis using US death certificates. Am J Human Genet. 2001;68:1110-1118
15. Evans DGR, Baser ME, Friedman JM, McGaughran J, Timms B, Moran A. Malignant peripheral nerve sheath tumors in neurofibromatosis 1. J Hum Genet. 2002;39(5):311-314
16. Mautner VF, Friedrich RE, Von Deimling A, Hagel C, Korf B, Knofel MT, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma. Neuroradiology. 2003;45(9):618-625
17. Ferner RE, Lucas JD, O’Doherty MJ, Hughes RA, Smith MA, Cronin BF, et al. Evaluation of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1. J Neurol Neurosurg Psychiatry. 2000;68(3):353-357
18. Korf BR. Malignancy in neurofibromatosis type 1. Oncologist. 2000;5(6):477-485
19. Listernick R, Louis DN, Packer RJ, Gutmann DH. Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 Optic Pathway Glioma Task Force. Ann Neurol. 1997;41(2):143-149
20. Listernick R, Charrow J, Greenwald M, Mets M. Natural history of optic pathway tumors in children with neurofibromatosis type 1: a longitudinal study. J Pediatr. 1994;125(1):63-66
21. Lewis RA, Gerson LP, Axelson KA, Riccardi VM, Whitford RP. von Recklinghausen neurofibromatosis II. Incidence of optic gliomata. Ophthalmology. 1984;91:929-935 Abstract |
22. Packer RJ. SLBLeal. Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update. Ann Neurol. 1988;23:79-85
23. Riccardi VM. The case for routine neuroimaging in neurofibromatosis. Neurofibromatosis. 1988;1:
24. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997;278(1):51-57
25. DiMario FJJ, Ramsby G. Magnetic resonance imaging lesion analysis in neurofibromatosis type 1. Arch Neurol. 1998;55(4):500-505
26. Es SV, North KN, McHugh K, Silva MD. MRI findings in children with neurofibromatosis type 1: a prospective study. Pediatr Radiol. 1996;26(7):478-487
27. Cutting LE, Koth CW, Burnette CP, Abrams MT, Kaufmann WE, Denckla MB. Relationship of cognitive functioning, whole brain volumes, and T2- weighted hyperintensities in neurofibromatosis-1. J Child Neurol. 2000;15(3):157-160
28. Denckla MB, Hofman K, Mazzocco MMM, Melhem E, Reiss AL, Bryan RN, et al. Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis-1. Am J Med Genet. 1996;67:98-102
29. Ferner RE, Chaudhuri R, Bingham J, Cox T, Hughes RAC. MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry. 1993;56:492-495
30. Hyman SL, Gill DS, Shores EA, Steinberg A, Joy P, Gibikote SV, et al. Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1. Neurology. 2003;60(7):1139-1145
31. North K, Hyman S, Barton B. Cognitive deficits in neurofibromatosis 1. J Child Neurol. 2002;17(8):605-612
32. Tinschert S, Naumann I, Stegmann E, Buske A, Kaufmann D, Thiel G, et al. Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene. Eur J Hum Genet. 2000;8(6):455-459
33. Vandenbroucke I, Van Doorn R, Callens T, Cobben JM, Starink TM, Messiaen L. Genetic and clinical mosaicism in a patient with neurofibromatosis type 1. Hum Genet. 2004;114(3):284-290
34. Lazaro C, Ravella A, Gaona A, Volpini V, Estivill X. Neurofibromatosis type 1 due to germ-line mosaicism in a clinically normal father [see comments]. N Engl J Med. 1994;331(21):1403-1407
35. Gutmann DH, Collins FS. The neurofibromatosis type 1 gene and its protein product, neurofibromin. Neuron. 1993;10:335-343
36. Cichowski K, Jacks T. NF1 tumor suppressor gene function: narrowing the GAP. Cell. 2001;104(4):593-604
37. Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat. 2000;15(6):541-555
38. Liebermann F, Korf BR. Emerging approaches toward the treatment of neurofibromatoses. Genet Med. 1999;1(4):158-164
39. Poussaint TY, Jaramillo D, Chang Y, Korf B. Interobserver reproducibility of volumetric MR imaging measurements of plexiform neurofibromas. AJR Am J Roentgenol. 2003;180(2):419-423
40. Neurofiromatosis type  I [Full text]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

March  6, 2010 — The failure of segmentation between the skull and first cervical vertebra results in assimilation of the atlas. The assimilation may be complete (Figs 1, 2) or partial. It invariably results in basilar invagination. Although the Wackenheim clivus baseline may be normal, the clivus-canal angle may be decreased. When incompletely assimilated, the atlas arches appear too high on the lateral plain radiograph or, when completely assimilated, are not visible at all (Fig 3). There is an increased prevalence of associated fusion of the axis and third cervical vertebra in association with atlantooccipital assimilation (3). When this is present, gradual loosening of the atlantodental joint with progressive atlantoaxial subluxation may occur, reported in approximately 50% of cases (Fig 4) (1,2). In some instances, atlantooccipital assimilation may be associated with sudden death (4).

Figures 1. Complete atlantooccipital assimilation. Coronal (a) and midsagittal (b) diagrams illustrate the occipital condyles (C), odontoid process (0), anterior atlas arch (A), and posterior atlas arch (P). (Click for more details)

Figure 2. Atlantooccipital assimilation. (a) Coronal polytomogram demonstrates complete fusion of the lateral C-1 masses (1) to the occipital condyles (0). (b) Midsagittal polytomogram reveals complete assimilation of the anterior arch (A) to the basion and probably the cortices of the posterior arch (dot) and the opisthion. (C) Coronal CT scans reveal complete assimilation of the lateral C-1 masses (1) and the occipital condyles (0). Eccentric positioning of the odontoid process at the C-1 level is demonstrated. (Click for more details)

Figure 3. Atlantooccipital assimilation. (a) On the lateral radiograph, the atlas arches and odontoid process are not clearly identified. Basilar invagination, however, is suggested by the location of the Chamberlain line (dotted line) in relation to the remainder of the axis (C2). (b) Reconstructed midsagittal CT scan reveals assimilation of the anterior atlas arch (A) to the basion (dot) and the posterior arch (P) to the opisthion (*). The tip of the odontoid (0) lies well above the Chamberlain line (extrapolated) and may also be fused with the anterior atlas arch. (c) Reconstructed coronal CT scan reveals complete fusion of the hypoplastic occipital condyles to the lateral C-1 masses. Note the upward medial slope to the skull base. (d) Midsagittal TI-weighted (600/20) MR image also reveals the anterior arch (single dot) fused to the basion (arrow) and the posterior arch (double dots) fused to the opisthion (*). The Chamberlain line (dashed line) is violated. (Click for more details)

Figure 4. Atlantooccipital assimilation with atlantoaxial subluxation. (a) Reconstructed midsagittal CT scan reveals complete atlas arch assimilation. The odontoid process (0 ) lies at the level of the foramen magnum. A = anterior arch, P = posterior arch. (b) Midsagittal TI-weighted (600/20) MR image reveals elongation and a ‘ ‘comma’ ‘ configuration to the anterior lip of the foramen magnum produced by incorporation of the anterior atlas arch to the basion (dot). A similar finding is present at the posterior margin of the foramen magnum. There is a marked increase in the anterior atlantodental interval (dotted line) such that the displaced odontoid process (0) is markedly compressing the cervicomedullary junction. Also note incomplete segmentation of C-2 and C-3. (Click for more details)

References

1. vonTorklus D, Gehle W. The upper cervical spine. NewYork, NY: Grune & Stratton, i972.
2. VanGilderJC, Menezes MI, Dolan KD. The craniovertebral junction and its abnormalities. New York, NY: Futura, 1987.
3. McRae DL, Barnum AS. Occipitalization of the atlas. AJR 1953; 70:23-46.
4. Vakili ST, AguilanJC, MullerJ. Sudden unexpected death associated with atlanto-occipital fusion. AmJ Forensic Med Pathol 1985; 6:39- 43.
5. Neuroimaging of congenital syringomyelia [Full text]
6. Case of the week…Multiple craniocervical anomalies [Click to download in PDF format]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

February 28, 2010 —  Muscle can react pathologically and radiographically in a limited number of ways. The cardinal radiologic abnormalities are changes in muscle size or shape (atrophy, hypertrophy, pseudohypertrophy, and mass) and altered signal intensity. Most neuromuscular conditions that result in MRI abnormalities cause changes primarily in signal intensity.

Chronic disorders, both myopathic and neurogenic, result in fatty deposition that causes increased signal on T1- and T2-weighted imaging. Although these hyperintensities cannot distinguish myopathic and neurogenic lesions definitively, when atrophy is seen in conjunction with T1 and T2 hyperintensities, a neurogenic cause is more likely. A chronic myopathic condition is more likely to cause no alteration in muscle bulk (see Fig. 1), although conditions such as inclusion body myositis (IBM), may not follow this rule of thumb. Acute denervation is unlikely to result in any MRI signal change on standard MRI sequences over the first week, similar to the delayed development of abnormal spontaneous activity during electromyography (EMG) [1]. Turbo inversion recovery magnitude imaging (TIRM), a newer and less available sequence, has revealed MRI abnormalities in mice as early as 24 hours after nerve transection [2]. TIRM imaging in 40 consecutive patients who had foot drop showed a high concordance with abnormalities during EMG [3]. Subacute denervation results in increased T2 signal from an increase in muscle proton relaxation time, although the reason for this change remains uncertain (Fig. 2). As denervation becomes more chronic, edema-like changes dissipate and fatty infiltration develops. Muscle atrophy also occurs commonly in this setting (Fig. 3).

Figure 1. This patient had progressive proximal muscle weakness; muscle biopsy performed early in the disease course revealed an inflammatory myopathy. She did not improve with immunosuppressive medications and later developed disproportionate involvement of the quadriceps musculature. IBM was suspected clinically, but the patient elected not to have another muscle biopsy. (A) T1-weighted images of the thigh reveal diffuse hyperintensity with relative sparing of the posterior thigh. These findings are indicative of fatty replacement. (B) T2-weighted images show a similar pattern of involvement. Because of the fatty replacement, no edema-like changes can be assessed. (C) STIR imaging removes the signal from fat, leaving any signal resulting from edema-like change. In this case of presumed end-stage muscle, no such changes were seen. (Click to enlarge figures)

Figure 2. This patient presented with pain in the shoulder and difficulty using the arm. EMG showed evidence of acute denervation in the infraspinatus muscle but not the supraspinatus, consistent with a partial suprascapular nerve lesion. (1) Proton density fat suppression study performed after arthrography showing paralabral cyst (A). (2) Proton density fat suppression study showing edema-like changes of the infraspinatus muscle (B) sparing the teres minor (C). (3) Proton density fat suppression study showing edema-like changes of the infraspinatus muscle (D) sparing the supraspinatus (E), subscapularis (F), and teres minor (G) muscles. These findings all support the diagnosis of a partial suprascapular nerve lesion with denervation solely of the infraspinatus muscle due to a paralabral cyst. (Click to enlarge figure)

Figure 3. (A) Elderly patient who had Charcot-Marie-Tooth disease type IA. T1-weighted imaging of the forelegs shows diffuse hyperintensities reflecting fatty infiltration of muscle, in this case as a result of denervation. Muscle atrophy also is present, although it may not be appreciated on MRI if not compared with normal muscle. (B) This patient’s 34-year-old daughter had no symptoms but had evidence of diffuse demyelinating neuropathy on electrodiagnostic testing. Genetic testing proved the diagnosis of Charcot-Marie-Tooth IA (this patient was the proband, presenting to medical attention for an unrelated condition). T1-weighted imaging shows no hyperintensities. Note the normal muscle mass compared with her mother’s. (Click to enlarge figures)

It originally was hoped that radiologic patterns of muscle involvement might prove diagnostic of specific muscle conditions. Certain myopathies do, in fact, have a predilection for specific muscle groups, such as the posterior compartment of the calf in Miyoshi myopathy (Fig. 5) and the finger flexor musculature in IBM (Fig. 5). Neurologic examination of most patients who have a myopathy shows nonspecific limb-girdle weakness, with a broad differential diagnosis. MRI can reveal edema-like changes with disproportionate involvement of individual muscles, even in conditions, such as polymyositis and dermatomyositis, that clinically involve all or most of the proximal musculature. As more cases are reported, the hope of a pure pattern-recognition approach has been dispelled. It now is recognized that there is remarkable variability in the distribution of muscles affected within the same condition. Moreover, the observed selective changes may result from different types of myopathy. When clear asymmetry is present, it can be helpful in limiting the differential diagnosis (Box 1). Selective muscle atrophy, as discussed previously, is an important diagnostic clue. Recognition of other MRI signs also can add valuable information. Observing fatty infiltration or edema-like changes can provide objective information about the chronicity of the process, which is helpful if the history is unreliable. Muscles with severe fatty infiltration should be avoided during biopsy, as these muscles are more likely to result in end-stage muscle, confounding a specific diagnosis in most cases.

Figure 4. This 55-year-old man had more than 30 years of progressive calf weakness. (A) T1-weighted imaging is consistent with fatty deposition confined to the calf musculature. (B) T2 fat suppression imaging is normal; no edema-like changes were present. Because of concerns about end-stage muscle in the gastrocnemius muscle, a vastus lateralis muscle biopsy was performed; immunohistochemical staining revealed absent sarcolemmal localization for dysferlin consistent with Miyoshi myopathy. (Click to enlarge figure)

Figure 5. This 72-year-old man complained of recent asymmetric weakness of the finger flexors. MRI was performed because of concerns of nerve entrapment. (A) T1 imaging of the forearm reveals fatty infiltration of the finger flexor musculature indicating a more chronic process. (B) T2 imaging cannot distinguish between fatty deposition and edema-like changes. STIR imaging would have been helpful but was not performed in this case. He was referred for neuromuscular evaluation and was found to have proximal weakness of the legs. Muscle biopsy was indicative of IBM. (Click to enlarge figure)

Box 1. Myopathies with significant asymmetry

Other features also are valuable in suggesting chronicity. In myopathies with an indolent onset and slow progression, muscle loss may occur so slowly that fatty deposition may mask any gross observation of muscle atrophy. In conditions, such as dystrophinopathy, pseudohypertrophy may occur (Fig. 6). MRI in these indolent myopathies shows a filled-up appearance of normal muscle size with fatty deposition [4]. Myopathies that are more acute in onset, such as inflammatory myopathy, do not reveal fatty deposition until the disease becomes chronic. Acutely, these conditions are more likely to result in focally atrophied muscle contours with undulation of the fascia (Fig. 7).

Figure 6. Pseudohypertrophy and the filling-up process. Patients who had dystrophinopathies (DMD in this figure) may exhibit atrophy, true hypertrophy, and pseudohypertrophy. (A) Symmetric, proximal diminution in thigh muscle volume (atrophy) is evident. Note prominence of gracilis (G) and sartorius (S) without fatty replacement (true hypertrophy). (B) In another patient, the thighs show relative sparing of some muscles, whereas muscles with extensive fat deposition maintain their normal size. This filling-up process is a hint that the disease process is more likely to be a slowly developing process. (C) Pseudohypertrophy with enlarged muscles occupied primarily by fat. (Click to enlarge figure)

Figure 7. This 54-year-old woman had rapidly progressive weakness, an elevated creatine kinase level, and myopathic features on her EMG. Proton density fat suppression imaging did not reveal any edema-like foci; vastus lateralis muscle biopsy revealed inflammatory myopathy. Note the undulating fascia bilaterally, suggesting relatively acute onset. (Click to enlarge figure)

In contrast, denervation is likely to cause atrophy on MRI. Even when atrophy cannot be detected on clinical examination, comparison of the affected to unaffected side on MRI may reveal evidence of atrophy. Comparison with nearby normal muscles also can be valuable in assessing muscle bulk. MRI is extremely accurate in measuring muscle mass, comparable to cadaveric measurements [5]. Because individual motor units are affected in denervating conditions, atrophy tends to be somewhat patchy, resulting in a moth-eaten appearance on MRI. As discussed previously, acute denervation does not cause signal abnormalities, but subacute denervation causes T2-weighted hyperintensities (see Fig. 3) that dissipate over 1 to 2 years. Chronic denervation results in T1-weighted hyperintensity representing fat deposition, often in association with muscle atrophy (Fig. 8).

Figure 8. This 32-year-old man presented with 2 years of painless weakness of the left calf. Electrodiagnostic studies revealed an isolated tibial mononeuropathy; no cause was ever found. MRI was performed to look for a mass compressing the tibial nerve. (A) T1 imaging shows diffuse fatty infiltration into the gastrocnemius and soleus muscles. (B) Proton density fat suppression imaging shows minimal edema-like changes; over time, edema-like changes dissipate in chronic denervation. Note the atrophy of the gastrocnemius muscle compared with the unaffected side. (Click to enlarge figure)

Although most primary neuromuscular disorders result in altered signal intensity, clinicians and radiologists who encounter MRI of the musculoskeletal system also must be aware of alterations in size and shape. Muscle atrophy can occur in denervation and some myopathic disorders, as discussed previously. Atrophy is recognized easily on MRI (Fig. 3 and Fig. 8) when muscle bulk is assessed properly; the degree of atrophy can be quantified accurately [5,6]. Although MRI quantification of atrophy has not been directly compared with clinical assessment, it is likely superior in certain scenarios. When one muscle becomes atrophic, a neighboring muscle may hypertrophy to compensate. Under these circumstances, the area of the total muscle group may remain unchanged, resulting in no obvious atrophy. Even without compensatory hypertrophy, when one individual muscle within a functional group (such as one member of the quadriceps musculature) becomes atrophic, the other muscles may shield the atrophic muscle from view. MRI allows direct visualization of the individual muscles, allowing detection of atrophy that may not be visible clinically. Comparison with normal surrounding muscles, and possibly contralateral muscles, may be required to assess the degree of atrophy. Atrophic muscle, especially in the distribution of one particular peripheral nerve, should alert the physician reviewing the images to the possibility of a compressive neuropathy.

When muscle bulk appears augmented (Box 2), the T1-weighted images should be examined for evidence of fat deposition, which suggests pseudohypertrophy. Duchenne and Becker muscular dystrophies are common causes of calf pseudohypertrophy. Amyloidosis [7] and limb-girdle muscular dystrophy types 1C, 2D, 2E, and 2I [8] also may cause pseudohypertrophy as a result of deposition within the muscle. True muscle hypertrophy, as discussed previously, can occur as a compensatory reaction to muscle atrophy within the same functional group. It can occur as sequelae of poliomyelitis or, rarely, radiculopathy. Muscle hypertrophy also can occur as a result of other unrelated diseases (Fig. 9). Several disorders associated with myotonia—myotonia congenita, paramyotonia congenita, myotonic dystrophy (DM) type II, Schwartz-Jampel syndrome, and hyperkalemic periodic paralysis—all can cause true hypertrophy. Acromegaly and Hoffman syndromes (hypothyroidism) are associated with muscle enlargement. Several infections (cysticercosis, trichinosis, and schistosomiasis) result in muscle enlargement; however, MRI shows focal lesions in these conditions, suggesting an external cause. Sarcoidosis also may result in muscle hypertrophy; approximately half the cases of sarcoidosis have muscle involvement on biopsy, even if no clinical evidence of myopathy is present. No study has been performed, however, to determine what percentage of patients who have sarcoidosis, either with or without muscular involvement, display MRI changes.

Box 2. Causes of muscle hypertrophy and pseudohypertrophy

Figure 9. The palmaris longus is one of the most variable muscles in the body. This 33-year-old woman presented with complaints of a painless mass in her distal right forearm. Coronal and axial MRI of the distal forearm demonstrates the palpable region of concern. Along the volar aspect of the distal forearm there is a soft tissue “mass” (outlined by arrows) not normally present. It is isointense to muscle on both T1-weighted (A, B) and T2-weighted fat suppressed (D, E) images. It contracts like muscle: (D) relaxed hand; (E) clenched fist. It is in the expected location of the palmaris longus muscle tendon (circled in a different patient) (C). This is consistent with an anomalous palmaris longus muscle. Usually, the muscle belly is proximal and the tendon distal in the forearm. In this case, the belly was distal and tendon proximal. R, radius; U, ulna. (Click to enlarge figure)

References

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