INTRODUCTION AND AIMS The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change... more INTRODUCTION AND AIMS The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change-sensitive tool for assessing the severity of neuropathy in children and adolescents between 3 and 20 years of age. The aim of this article is to translate and validate a Spanish version of the CMTPedS in order to disseminate its use in Spanish-speaking countries. MATERIALS AND METHODS The process used to translate the CMTPedS into Spanish was the reverse parallel translation method based on the principles of good practice for translation and the cultural adaptation process of the Food and Drug Administration Guidelines. A direct translation of the original source of the CMTPedS into Spanish was performed first and reviewed by experts in Charcot-Marie-Tooth (CMT) disease trained in the use of the CMTPedS tool. The Spanish version was then translated back into English by a linguist specialised in translation. RESULTS The preliminary Spanish version of the CMTPedS was evaluated in 18 child...
Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, i... more Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG.
Mutations in the BICD2 gene cause autosomal dominant lower extremity‐predominant spinal muscular ... more Mutations in the BICD2 gene cause autosomal dominant lower extremity‐predominant spinal muscular atrophy 2A (SMALED2A), a condition that is associated with a specific pattern of thigh and calf muscle involvement when studied by magnetic resonance imaging (MRI). Patients may present minor clinical sensory impairment, but objective sensory involvement has yet to be demonstrated.
The current study was designed to determine the risk of developing clinically definite multiple s... more The current study was designed to determine the risk of developing clinically definite multiple sclerosis (CDMS) after an isolated idiopathic optic neuritis (ON). We retrospectively studied 28 patients (range from 18-45 years) who presented a unilateral acute ON between 1 st April and 31 st December. We excluded optic neuropathy of other causes, a previous diagnosis of MS or systemic diseases associated with ON. Patients underwent brain MRI, visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs). The mean interval between ON onset and MRI was 3.1 months. 24 patients were treated with corticosteroids in different ways: oral prednisone (14) and intravenous methylprednisolone (10). Mean duration of the follow-up was 4.5 years in 26 patients. Brain MRI detected white matter areas with increased signal in 10 of 25 patients (40%). Eight (30%) had bilateral anormalities on VEP, while SEPs and BAEPs revealed anormalities in o...
Charcot-Marie-Tooth disease (CMT) is a hereditary motor-sensory neuropathy with a large genetic h... more Charcot-Marie-Tooth disease (CMT) is a hereditary motor-sensory neuropathy with a large genetic heterogeneity. Type 1 (CMT1), or demyelinating CMT, and type 2 (CMT2), or neuronal CMT, are two genetically and clinically distinct entities. CMT1 is the more prevalent and better understood of the two from a genetic standpoint. At least three genes have been shown to be implicated: the 22Kda (PMP22) gene for peripheral myelin protein located in the 17p11.2 chromosome (the CMT1A locus), the P0 myelin protein gene located in the 1q23 chromosome (the CMT1B locus), and the connexin 32 (Cx32) gene located in the Xq13 chromosome (CMTX locus). The most common mutation in CMT1, found in 70% of cases, is a tandem duplication of 1,500 kb at the CMT1A locus. Point mutations have also been described in the PMP22 gene and in P0 and Cx32. Déjerine-Sortas syndrome (DSS) is caused by point mutations in PMP22 and P0 genes, whereas familial neuropathy with liability to pressure palsies (FNPP) or tomacular...
We have carried out a hearing study with pure tone audiometry and ABR of 39 patients affected by ... more We have carried out a hearing study with pure tone audiometry and ABR of 39 patients affected by hereditary motor and sensory neuropathy or Charcot-Marie Tooth disease. We have noticed a hearing deficiency in a significant percentage of cases (28%). We attribute the abnormalities to disorders in the area of the VIIIth nerve and of the brainstem. No significant differences appear in the results obtained between patients belonging to type I and patients belonging to type II of this disease.
Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (H... more Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are two inherited peripheral neuropathies. The most prevalent mutations are a reciprocal 1.5-Mb duplication and 1.5-Mb deletion, respectively, at the CMT1A/HNPP locus on chromosome 17p11.2. Point mutations in the coding region of the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT patients, including CMT type 1 (CMT1), CMT type 2 (CMT2) and Déjérine-Sottas neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families lacking a deletion. We have investigated point and small mutations in the MPZ, PMP22 and Cx32 genes in a series of patients of Spanish ancestry: 47 CMT patients without duplications, and 5 HNPP patients without deletions. We found 15 different mutations in 16 CMT patients (34%). Nine different mutations in ten patients were detected in the Cx32 gene, this being the most frequently involved gene in this series, whereas five mutations involved the MPZ gene and only one the PMP22 gene. Six out of nine nucleotide substitutions in the Cx32 gene involved two codons encoding arginine at positions 164 and 183, suggesting that these two codons may constitute two Cx32 regions prone to mutate in the Spanish population. Analysis of HNPP patients revealed a 5' splicing mutation in intron 1 of the PMP22 gene in a family with autosomal dominance, which confirms allelic heterogeneity in HNPP. Ectopic mRNA analysis on leukocytes suggests that this mutation might behave as a null allele.
Five cases of acute disseminated encephalomyelitis (ADE) with a follow-up longer than 5 years are... more Five cases of acute disseminated encephalomyelitis (ADE) with a follow-up longer than 5 years are presented. The clinical picture, CT images, MR and laboratory tests, specially LCR and evoked potentials presented in a variable form. In two cases the symptoms were preceded by viral infection. The course was acute in one case while the other four evolved in a subacute form during weeks. In two patients a pseudotumoral pattern was observed in the CT and MR images leading to difficulties in the diagnosis. Clinical improvement was accompanied by a partial resolution of the lesions. Steroid treatment improved symptomatology in all the cases. Knowledge of this process may avoid the unnecessary practice of other, more aggressive tests.
BACKGROUND The Charcot-Marie-Tooth (CMT) disease or hereditary motor-sensitive neuropathy (HMSN) ... more BACKGROUND The Charcot-Marie-Tooth (CMT) disease or hereditary motor-sensitive neuropathy (HMSN) is the most frequent hereditary neuropathy. The demyelinated or type 1 form (CMT1) is the most frequently presented, commonly being of a dominant autosomic inheritance. CMT1 is heterogeneous genetically and the subjacent mutation found in most of the cases is a duplication of 1,500 kb in the CMT1A locus of chromosome 17p11.2. The aim of the present study was to determine the prevalence of CMT1A duplication in patients with CMT1 and evaluate its usefulness as a biological diagnostic marker. METHODS The study was carried out in a group of patients with HMSN who were not related, and were distributed according to the following diagnostic categories: CMT1 (n = 49), CMT2 (n = 9), untyped CMT (n = 11) and Déjérine-Sottas (DS) disease (n = 4). To detect three alleles confirming the presence of duplication the DNA of the patients was analyzed with four polymorph markers, VAW409R3a, RM11-GT, VAW4...
Chronic spinal muscular atrophy usually presents in childhood or adolescence, generally as predom... more Chronic spinal muscular atrophy usually presents in childhood or adolescence, generally as predominant proximal muscle weakness. Other less common forms involving distal muscles can be either partial or generalized and their prognosis is relatively good. At least three well-defined types can be identified: a) a form located in the upper extremities that typically affects young men, is not familial and is highly prevalent in Asia; b) a more generalized form that can be either familial or isolated and that resembles Charcot-Marie-Tooth disease in the distribution of muscle weakness and prognosis, and c) another generalized form that starts in and mainly involves the upper extremities, is inherited in an autosomal dominant manner and is accompanied by laryngeal involvement. We review the literature and describe 27 patients with distal spinal muscular atrophy resembling Charcot-Marie-Tooth disease.
Laing distal myopathy have been identified in families and sporadic cases around the world. Howev... more Laing distal myopathy have been identified in families and sporadic cases around the world. However, there are still undetermined issues such the spectrum of clinical phenotype, the concurrence of cardiomyopathy and the profile of pathological findings. We report a large cluster of patients, with distal myosinopathy, originating from La Safor region, Spain, due to K1729del mutation in the MYH7 gene. Starting from 7 index cases, 4 unrelated pedigrees were built up. Seventy five individuals were examined and 32 of them were affected; information from additional 27 deceased or not yet examined patients were also recorded. Clinical data, CK levels, EKG, echocardiography, electrophysiologic tests, muscle MRI/TC and muscle biopsies were analyzed. Sequencing of exon 36 of MYH7 gene and haplotype analyses were performed. Age at onset ranged from congenital to 50’s. All patients had anterior compartment muscle weakness and most of them had neck flexor, finger extensor and mild facial weaknes...
INTRODUCTION AND AIMS The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change... more INTRODUCTION AND AIMS The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change-sensitive tool for assessing the severity of neuropathy in children and adolescents between 3 and 20 years of age. The aim of this article is to translate and validate a Spanish version of the CMTPedS in order to disseminate its use in Spanish-speaking countries. MATERIALS AND METHODS The process used to translate the CMTPedS into Spanish was the reverse parallel translation method based on the principles of good practice for translation and the cultural adaptation process of the Food and Drug Administration Guidelines. A direct translation of the original source of the CMTPedS into Spanish was performed first and reviewed by experts in Charcot-Marie-Tooth (CMT) disease trained in the use of the CMTPedS tool. The Spanish version was then translated back into English by a linguist specialised in translation. RESULTS The preliminary Spanish version of the CMTPedS was evaluated in 18 child...
Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, i... more Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG.
Mutations in the BICD2 gene cause autosomal dominant lower extremity‐predominant spinal muscular ... more Mutations in the BICD2 gene cause autosomal dominant lower extremity‐predominant spinal muscular atrophy 2A (SMALED2A), a condition that is associated with a specific pattern of thigh and calf muscle involvement when studied by magnetic resonance imaging (MRI). Patients may present minor clinical sensory impairment, but objective sensory involvement has yet to be demonstrated.
The current study was designed to determine the risk of developing clinically definite multiple s... more The current study was designed to determine the risk of developing clinically definite multiple sclerosis (CDMS) after an isolated idiopathic optic neuritis (ON). We retrospectively studied 28 patients (range from 18-45 years) who presented a unilateral acute ON between 1 st April and 31 st December. We excluded optic neuropathy of other causes, a previous diagnosis of MS or systemic diseases associated with ON. Patients underwent brain MRI, visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs). The mean interval between ON onset and MRI was 3.1 months. 24 patients were treated with corticosteroids in different ways: oral prednisone (14) and intravenous methylprednisolone (10). Mean duration of the follow-up was 4.5 years in 26 patients. Brain MRI detected white matter areas with increased signal in 10 of 25 patients (40%). Eight (30%) had bilateral anormalities on VEP, while SEPs and BAEPs revealed anormalities in o...
Charcot-Marie-Tooth disease (CMT) is a hereditary motor-sensory neuropathy with a large genetic h... more Charcot-Marie-Tooth disease (CMT) is a hereditary motor-sensory neuropathy with a large genetic heterogeneity. Type 1 (CMT1), or demyelinating CMT, and type 2 (CMT2), or neuronal CMT, are two genetically and clinically distinct entities. CMT1 is the more prevalent and better understood of the two from a genetic standpoint. At least three genes have been shown to be implicated: the 22Kda (PMP22) gene for peripheral myelin protein located in the 17p11.2 chromosome (the CMT1A locus), the P0 myelin protein gene located in the 1q23 chromosome (the CMT1B locus), and the connexin 32 (Cx32) gene located in the Xq13 chromosome (CMTX locus). The most common mutation in CMT1, found in 70% of cases, is a tandem duplication of 1,500 kb at the CMT1A locus. Point mutations have also been described in the PMP22 gene and in P0 and Cx32. Déjerine-Sortas syndrome (DSS) is caused by point mutations in PMP22 and P0 genes, whereas familial neuropathy with liability to pressure palsies (FNPP) or tomacular...
We have carried out a hearing study with pure tone audiometry and ABR of 39 patients affected by ... more We have carried out a hearing study with pure tone audiometry and ABR of 39 patients affected by hereditary motor and sensory neuropathy or Charcot-Marie Tooth disease. We have noticed a hearing deficiency in a significant percentage of cases (28%). We attribute the abnormalities to disorders in the area of the VIIIth nerve and of the brainstem. No significant differences appear in the results obtained between patients belonging to type I and patients belonging to type II of this disease.
Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (H... more Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are two inherited peripheral neuropathies. The most prevalent mutations are a reciprocal 1.5-Mb duplication and 1.5-Mb deletion, respectively, at the CMT1A/HNPP locus on chromosome 17p11.2. Point mutations in the coding region of the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT patients, including CMT type 1 (CMT1), CMT type 2 (CMT2) and Déjérine-Sottas neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families lacking a deletion. We have investigated point and small mutations in the MPZ, PMP22 and Cx32 genes in a series of patients of Spanish ancestry: 47 CMT patients without duplications, and 5 HNPP patients without deletions. We found 15 different mutations in 16 CMT patients (34%). Nine different mutations in ten patients were detected in the Cx32 gene, this being the most frequently involved gene in this series, whereas five mutations involved the MPZ gene and only one the PMP22 gene. Six out of nine nucleotide substitutions in the Cx32 gene involved two codons encoding arginine at positions 164 and 183, suggesting that these two codons may constitute two Cx32 regions prone to mutate in the Spanish population. Analysis of HNPP patients revealed a 5' splicing mutation in intron 1 of the PMP22 gene in a family with autosomal dominance, which confirms allelic heterogeneity in HNPP. Ectopic mRNA analysis on leukocytes suggests that this mutation might behave as a null allele.
Five cases of acute disseminated encephalomyelitis (ADE) with a follow-up longer than 5 years are... more Five cases of acute disseminated encephalomyelitis (ADE) with a follow-up longer than 5 years are presented. The clinical picture, CT images, MR and laboratory tests, specially LCR and evoked potentials presented in a variable form. In two cases the symptoms were preceded by viral infection. The course was acute in one case while the other four evolved in a subacute form during weeks. In two patients a pseudotumoral pattern was observed in the CT and MR images leading to difficulties in the diagnosis. Clinical improvement was accompanied by a partial resolution of the lesions. Steroid treatment improved symptomatology in all the cases. Knowledge of this process may avoid the unnecessary practice of other, more aggressive tests.
BACKGROUND The Charcot-Marie-Tooth (CMT) disease or hereditary motor-sensitive neuropathy (HMSN) ... more BACKGROUND The Charcot-Marie-Tooth (CMT) disease or hereditary motor-sensitive neuropathy (HMSN) is the most frequent hereditary neuropathy. The demyelinated or type 1 form (CMT1) is the most frequently presented, commonly being of a dominant autosomic inheritance. CMT1 is heterogeneous genetically and the subjacent mutation found in most of the cases is a duplication of 1,500 kb in the CMT1A locus of chromosome 17p11.2. The aim of the present study was to determine the prevalence of CMT1A duplication in patients with CMT1 and evaluate its usefulness as a biological diagnostic marker. METHODS The study was carried out in a group of patients with HMSN who were not related, and were distributed according to the following diagnostic categories: CMT1 (n = 49), CMT2 (n = 9), untyped CMT (n = 11) and Déjérine-Sottas (DS) disease (n = 4). To detect three alleles confirming the presence of duplication the DNA of the patients was analyzed with four polymorph markers, VAW409R3a, RM11-GT, VAW4...
Chronic spinal muscular atrophy usually presents in childhood or adolescence, generally as predom... more Chronic spinal muscular atrophy usually presents in childhood or adolescence, generally as predominant proximal muscle weakness. Other less common forms involving distal muscles can be either partial or generalized and their prognosis is relatively good. At least three well-defined types can be identified: a) a form located in the upper extremities that typically affects young men, is not familial and is highly prevalent in Asia; b) a more generalized form that can be either familial or isolated and that resembles Charcot-Marie-Tooth disease in the distribution of muscle weakness and prognosis, and c) another generalized form that starts in and mainly involves the upper extremities, is inherited in an autosomal dominant manner and is accompanied by laryngeal involvement. We review the literature and describe 27 patients with distal spinal muscular atrophy resembling Charcot-Marie-Tooth disease.
Laing distal myopathy have been identified in families and sporadic cases around the world. Howev... more Laing distal myopathy have been identified in families and sporadic cases around the world. However, there are still undetermined issues such the spectrum of clinical phenotype, the concurrence of cardiomyopathy and the profile of pathological findings. We report a large cluster of patients, with distal myosinopathy, originating from La Safor region, Spain, due to K1729del mutation in the MYH7 gene. Starting from 7 index cases, 4 unrelated pedigrees were built up. Seventy five individuals were examined and 32 of them were affected; information from additional 27 deceased or not yet examined patients were also recorded. Clinical data, CK levels, EKG, echocardiography, electrophysiologic tests, muscle MRI/TC and muscle biopsies were analyzed. Sequencing of exon 36 of MYH7 gene and haplotype analyses were performed. Age at onset ranged from congenital to 50’s. All patients had anterior compartment muscle weakness and most of them had neck flexor, finger extensor and mild facial weaknes...
Uploads
Papers by T. Sevilla