on Neuromuscular disorders : NMD
by Cutellè C, Rastelli E, Gibellini M, Greco G, Frezza E, Botta A, Terracciano C, Massa R
We aimed to validate the Nine Hole Peg Test as a measure of dexterity in myotonic dystrophy type 1 (DM1). Fifty patients with adult-onset, genetically confirmed DM1 were evaluated by Nine Hole Peg Test and re-evaluated at one week. Myotonia was not a limiting factor. The first test was compared with that performed by normal subjects (n = 28). Contextually, patients underwent handgrip and three-finger pinch assessments by handheld dynamometer. The Nine Hole Peg Test showed high intra-rater and inter-rater reliability in DM1 [ICC 0.86/0.83 for dominant and 0.90/0.88 for non-dominant hand, respectively]. Inverse correlation with handgrip and pinch strength values (r = -0.4; p < 0.01) and direct correlation with Muscular Impairment Rating Scale (r = 0.4; p < 0.01) were found for both DH and NDH. The test was able to differentiate severe DM1 patients, stratified by extent of muscle impairment, from mildly affected and normal controls, with a sensitivity of 97% and 95% for dominant hand and non-dominant hand, respectively (p < 0.0001). In conclusion, we showed that the Nine Hole Peg Test is a reliable, valid and sensitive test of dexterity in DM1, and that it can be considered as a candidate outcome measure to monitor natural history of disease and, possibly, therapeutic response in clinical trials.
on Case reports in neurological medicine
by Frezza E, Terracciano C, Giacanelli M, Rastelli E, Greco G, Massa R
Pompe disease is an autosomal recessive disorder characterized by deficiency of alpha-glucosidase, a lysosomal enzyme, which can lead to glycogen accumulation in skeletal muscle, heart, and nervous system. Clinical presentation is highly variable, with infantile and late-onset (LOPED) forms. Although muscle biopsy findings are rather stereotyped, atypical features have been described. A 52-year-old man without a family history of muscle disorders presented with slowly progressing upper and lower limb girdle weakness and hyperCKemia. At needle EMG, a diffuse neurogenic pattern was detected. Muscle biopsy showed a selective type 1 fiber atrophy with vacuoles of various sizes, filled with PAS and acid phosphatase positive material, confirmed to be glycogen by electron microscopy (EM). Many atrophic fibers contained foci of myofibrillar material recognized as nemaline bodies (NBs) at EM. Low level of alpha-glucosidase activity in blood and molecular genetic testing confirmed the diagnosis of late-onset Pompe disease (LOPED). Major causes of hereditary and acquired NB myopathy were ruled out. In conclusion, NBs represent a novel histological finding in LOPED and characterize the atypical presentation of our case.
on Muscle & nerve
by Vizzaccaro E, Terracciano C, Rastelli E, Massa R
Aquaporins (AQPs) are a family of transmembrane proteins involved in the maintenance of osmotic gradients. AQP4 is abundant in skeletal muscle, where it seems to be associated with glycolytic metabolism. We investigated the pattern of expression of AQP4 in normal human myofibers relative to the main forms of myosin heavy chain (MHC).
on Ultrastructural pathology
by Terracciano C, Pachatz C, Rastelli E, Pastore FS, Melone MAB, Massa R
Plexiform neurofibroma is pathognomonic of neurofibromatosis 1 (NF1). An NF1-associated peripheral neuropathy has been described in a small minority of NF1 patients but its histopathological features are poorly characterized. We report the case of a 46-year-old woman presenting with bilateral supraclavicular painful masses without other stigmata of NF1. MRI showed bilateral plexiform lesions extending from cervical roots to the elbows. Nerve conduction studies documented a sensory motor polyneuropathy. Morphometric analysis of sural nerve biopsy showed a preferential loss of large-caliber myelinated fibers with a g ratio of 0.515, and the presence of regeneration clusters. By electron microscopy, marked and diffuse endoneurial fibrosis with an altered relationship between Schwann cells (SC) and collagen fibrils was observed. Moreover both myelinating and non-myelinating SC were characterized by the presence of various cell degradation products. These changes suggest that, in neurofibromatous neuropathy, a widespread axonal atrophy and degeneration take place independently on the presence of tumoral infiltration, possibly due to an impairment in SC-axon cross talk. In this case, the coexistence of plexiform neurofibromas with a peripheral neuropathy strongly suggests a diagnosis of NF1 even without fulfillment of clinical criteria. We propose that in the presence of plexiform neurofibromas, electrophysiological studies should be performed also in asymptomatic patients, in order to detect the existence of a subclinical neuropathy.
on Journal of neurology, neurosurgery, and psychiatry
by Terracciano C, Farina O, Esposito T, Lombardi L, Napolitano F, De Blasiis P, Ciccone G, Todisco V, Tuccillo F, Bernardini S, Di Iorio G, Melone MAB, Sampaolo S
on Journal of cellular physiology
by Pascarella A, Terracciano C, Farina O, Lombardi L, Esposito T, Napolitano F, Franzese G, Panella G, Tuccillo F, la Marca G, Bernardini S, Boffo S, Giordano A, Melone MAB, Di Iorio G, Sampaolo S
Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-α-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring. GAA activity, measured on dried blood spot (DBS) in all patients inversely correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3 different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD offspring. These latter resulted to have all a single GAA mutation but low GAA levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing both compound heterozygous and heterozygous GAA carriers. The other myopathies with more than 4 PAS-positive lymphocytes appeared to be all related to impaired autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes formation. Quantification of PAS-positive lymphocytes in blood films is useful to identify autophagic vacuolar myopathies and should be routinely used as first level test for Pompe disease. This article is protected by copyright. All rights reserved.
on Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia
by Campione E, Ventura A, Garofalo V, Torti C, Massa R, Terracciano C, Orlandi A, Bianchi L
on Neuromuscular disorders : NMD
by Campione E, Botta A, Di Prete M, Rastelli E, Gibellini M, Petrucci A, Bernardini S, Novelli G, Bianchi L, Orlandi A, Massa R, Terracciano C
Skin changes have been described in myotonic dystrophy type 1 (DM1). However, whether and in which way skin is a target of specific disease alterations in DM1 and DM2 has not been yet clarified. This study aims to explore cutaneous features of DM1 and DM2 patients. Skin examination was performed in 60 DM1, 15 DM2, and 103 control, unselected patients by means of dermoscopy. It revealed quantitative and qualitative abnormalities of nevi and typical signs of premature aging in both DM1 and DM2 patients, with a significantly higher frequency of dysplastic nevi, alopecia, xerosis and seborrheic dermatitis. Twenty-eight nevi were excised in DM patients and none showed histological features of melanoma, although 12 of them were diagnosed as dysplastic and the remaining 16 presented histological irregularity in melanin distribution. In DM1 patients, the number of nevi correlated with CTG expansion size, whereas the presence of dysplastic nevi and xerosis inversely correlated with vitamin D levels. DM1 and DM2 patients display a high frequency of skin abnormalities, the most common of which correlate with genotype severity and serum vitamin D levels. Skin examination is highly informative in these patients and reveals features suggestive of premature aging and impaired vitamin D homeostasis.
on Clinical neurology and neurosurgery
by Bombelli F, Lispi L, Porrini SC, Giacanelli M, Terracciano C, Massa R, Petrucci A
Weakness and fatigue are frequent symptoms in myotonic dystrophy type 1 (DM1), mainly as a result of muscle impairment. However, neuromuscular junction (NMJ) abnormalities could play an additional role in determining these manifestations. We aimed to document the possible NMJ involvement in DM1.
on Muscle & nerve
by Massa R, Pozzessere S, Rastelli E, Serra L, Terracciano C, Gibellini M, Bozzali M, Arca M
Neutral lipid-storage disease with myopathy is caused by mutations in PNPLA2, which produce skeletal and cardiac myopathy. We report a man with multiorgan neutral lipid storage and unusual multisystem clinical involvement, including cognitive impairment.