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... 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...
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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.
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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... 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.
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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... 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...
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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.... 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...
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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... 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.
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Research Interests: Genetics, Biology, Biological Sciences, Brain, Humans, and 15 moreChild, Haplotypes, Female, Infant, CHarcot Marie Tooth, Amino Acid Substitution Rates, Allele, Charcot Marie Tooth Disease, Axons, Age of Onset, DNA mutational analysis, Child preschool, alleles, Demyelinating diseases, and frameshift mutation
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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,... 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.
Research Interests: Genetics, Human Genetics, Complementary and Alternative Medicine, Biology, Medicine, and 15 moreHumans, Mutation, Female, Male, Pedigree, Peripheral Neuropathy, Myelin Proteins, Genetic Polymorphism, Charcot Marie Tooth Disease, DNA mutational analysis, Nucleotide substitution, Connexins, Autosomal Dominant, Mutation analysis, and Paediatrics and reproductive medicine
Research Interests: Cognitive Science, Neurology, Medicine, Spain, Muscle strength, and 14 moreSpinal Muscular Atrophy, Humans, Mutation, Female, Male, Clinical Sciences, Longitudinal Studies, Tooth Disease, Retrospective Studies, Myelin Proteins, Charcot Marie Tooth Disease, Neurosciences, DNA mutational analysis, and Connexins
Research Interests: Cognitive Science, Neurology, Medicine, Spain, Muscle strength, and 14 moreSpinal Muscular Atrophy, Humans, Mutation, Female, Male, Clinical Sciences, Longitudinal Studies, Tooth Disease, Retrospective Studies, Myelin Proteins, Charcot Marie Tooth Disease, Neurosciences, DNA mutational analysis, and Connexins
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... 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.
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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... 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...
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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... 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.
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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... 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...
Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a path- ogenic connection. The object of the... more
Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a path- ogenic connection. The object of the study is to investigate the prevalence of right-to-left shunt (RLS) in a cohort of patients suffering migraine with aura (MA) and its possible asso- ciation with migraine attacks triggered by VPA. We investigated the circum- stances triggering the migraine attacks, in a consecutive series of 72 MA patients and in a series of migraine without aura age and gen- der-matched. The presence and extent of RLS was assessed by transcranial
INTRODUCTION The high prevalence of patent foramen ovale in migraine with aura (MWA) seems to be well established; yet, the possible relation between the magnitude of the right-to-left shunt (RLS) and MWA is not so clear. As a hypothesis,... more
INTRODUCTION The high prevalence of patent foramen ovale in migraine with aura (MWA) seems to be well established; yet, the possible relation between the magnitude of the right-to-left shunt (RLS) and MWA is not so clear. As a hypothesis, if the RLS played a precipitating role, subjects with a larger degree of shunt might experience a higher number of seizures. We examine this possible relationship between the magnitude of the shunt and the incidence of seizures. PATIENTS AND METHODS We examined a series of 72 patients with MWA to obtain the frequencies of seizures (dividing them into three groups of increasing frequency), history and precipitating factors. The presence and magnitude of the RLS were later determined by means of transcranial Doppler ultrasonography, following a method that had previously been validated. Univariate analysis was then used to evaluate the possible association between the magnitude of the shunt and the frequency of seizures. RESULTS The mean age was 36 y...
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Mutations in the early growth response 2 gene (EGR2) cause demyelinating, but also axonal, neuropathies differing in severity and age of onset. Except for one family, all reported cases have autosomal dominant inheritance and mutations... more
Mutations in the early growth response 2 gene (EGR2) cause demyelinating, but also axonal, neuropathies differing in severity and age of onset. Except for one family, all reported cases have autosomal dominant inheritance and mutations are localized within the three zinc finger (ZNF) DNA‐binding domain. The aim of this study was to provide a clinical and molecular analysis of a novel recessive mutation in EGR2.
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OBJECTIVE To describe the fasciculation pattern in ALS and to analyse its clinical and pathophysiological significance. METHODS Ultrasound of 19 muscles was performed in 44 patients with a recent diagnosis (<90 days) of ALS. The number... more
OBJECTIVE To describe the fasciculation pattern in ALS and to analyse its clinical and pathophysiological significance. METHODS Ultrasound of 19 muscles was performed in 44 patients with a recent diagnosis (<90 days) of ALS. The number of fasciculations was recorded in each muscle and the muscle thickness and strength were additionally measured in limb muscles. A subgroup of patients were electromyographically assessed. RESULTS US was performed in 835 muscles and EMG was available in 263 muscles. US detected fasciculations more frequently than EMG. Fasciculations were widespread, especially in upper limbs onset patients and in the cervical region. Fasciculations' number inversely associated with ALSFR-R and body mass index (BMI) and directly with BMI loss and upper motor neuron (UMN) impairment. Our statistical model suggest that fasciculations increase with the initial lower motor neuron (LMN) degeneration, reach their peak when the muscle became mildly to moderately weak, decreasing afterwards with increasing muscle weakness and atrophy. CONCLUSIONS Our study suggests that both UMN and LMN degeneration trigger fasciculations causing BMI loss. The degree of LMN impairment could account for differences in fasciculations' rates within and between muscles. SIGNIFICANCE In ALS, fasciculations could explain the link between hyperexcitability and BMI loss.
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Background / Purpose: The pauci-symptomatic and asymptomatic hyperCKemia are syndromes that may represent a muscle disease in a benign or pre-clinical stage. They are often idiopathic and generate uncertainty about the long-term... more
Background / Purpose: The pauci-symptomatic and asymptomatic hyperCKemia are syndromes that may represent a muscle disease in a benign or pre-clinical stage. They are often idiopathic and generate uncertainty about the long-term prognosis. The aim of this study is to analyze a series of 188 cases which have been studied with muscle biopsy.Patients referred to our clinic with serum CK levels above 340 IU /l in which primary causes of their hyperCKemia have been ruled out. We performed a histological and immunohistochemical and protein analysis by immunoblotting. Main conclusion: The series consists of 148 men and 40 women, distributed as 10 childhood forms, 72 juveniles and 106 adults; 48 of them asymptomatic and 139 paucisymtomatic. Of the whole series 12 cases are familial; these include two patients from a family with a mutation in the RYR1 gene discovered after discovering a family member with hyperthermia, and 10 cases of hyperCKemia related to taking statins and persisting afte...
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Charcot-Marie-Tooth disease (CMTD) or hereditary motor and sensory neuropathy shows great genetic heterogeneity. The type 1 (CMT-1) or demyelinating form and the type 2 (CMT-2) or neuronal form are two clinically and genetically distinct... more
Charcot-Marie-Tooth disease (CMTD) or hereditary motor and sensory neuropathy shows great genetic heterogeneity. The type 1 (CMT-1) or demyelinating form and the type 2 (CMT-2) or neuronal form are two clinically and genetically distinct forms. Apart from the above mentioned motor and sensory forms, there is another type of neuropathy in which the clinical and neurophysiological involvement is exclusively motor and is known as distal spinal atrophy or hereditary distal motor neuropathy (HDMN), which is a syndrome to be included among the CMTD. The CMT-1 is the most prevalent form and the best understood from the genetic point of view. At least four genes have been reported to be involved: the gene for 22 kDa peripheral myelin protein (PMP-22), situated on the 17p11.2 chromosome (locus CMT-1A); the gene for myelin 0 protein situated on chromosome 1q23 (locus CMT-1B); the gene for conexine 32 (Cx32), found on chromosome Xq13 (locus CMT-X) and the gene EGR2 found on chromosome 10q21.1-...
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Molecular genetic research is leading to the continuous discovery of new genes and protein involved in peripheral nerves function. Simultaneously, extended clinical, neurophysiological and pathological research has yielded new... more
Molecular genetic research is leading to the continuous discovery of new genes and protein involved in peripheral nerves function. Simultaneously, extended clinical, neurophysiological and pathological research has yielded new genotype-phenotype correlation on Charcot-Marie-Tooth disease (CMT). This has made it possible to know that several genes can cause both demyelinating (CMT1) and axonal (CMT2) phenotypes. Those observations have questioned the validity of some current criteria for CMT classification and raise the need for new strategies for diagnosis. The discovery of Schwann cell-axon interaction is a challenge for coming years. In this review, we extensively analyzed mutations of genes that give rise to CMT1 or CMT2 phenotypes. There are at least three forms of genetic variability. MPZ gene mutations yield a real allelism, that is, CMT1 or CMT phenotypes associated to specific mutation by site or quality. GADP1 and probably NF-L gene manifest different phenotypes but only in...
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The aim of this study was to determine phenotypie characteristics of patients with early onset cerebellar ataxia (EOCA) with preserved tendon reflexes. The series comprises 25 patients, representing 10% of all ataxic patients who have... more
The aim of this study was to determine phenotypie characteristics of patients with early onset cerebellar ataxia (EOCA) with preserved tendon reflexes. The series comprises 25 patients, representing 10% of all ataxic patients who have been genetically studied in our laboratory since 1990. There were 11 males and 14 females. Fourteen patients were homozygous for the GAA expansion on chromosome 9q13 (group 1) and therefore a diagnosis of Friedreich's ataxia with retained reflexes (FARR) was given. The remaining 11 patients had two normal non-expanded alleles (group 2) and a working diagnosis of EOCA with retained reflexes (EOCARR) was established. Mean ages of onset were 13.7 +/- 5.9 years (3-25) for group 1 and 10.3 +/- 7.3 for group 2; the difference was not significant. Frequencies of symptoms and signs were also comparable for both groups the only significant differences being the higher frequency of nystagmus, cardiomyopathy and sensory neuropathy in group 1 patients. There w...
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A three-generation family affected by axonal Charcot-Marie-Tooth disease (CMT) was investigated with the aim of discovering genetic defects and to further characterize the phenotype. The clinical, nerve conduction studies and muscle... more
A three-generation family affected by axonal Charcot-Marie-Tooth disease (CMT) was investigated with the aim of discovering genetic defects and to further characterize the phenotype. The clinical, nerve conduction studies and muscle magnetic resonance images of the patients were reviewed. A whole exome sequencing was performed and the changes were investigated by genetic studies, in silico analysis and luciferase reporter assays. A novel c.1226G&gt;A change (p.R409Q) in the EGR2 gene was identified. Patients presented with a typical, late-onset axonal CMT phenotype with variable severity that was confirmed in the ancillary tests. The in silico studies showed that the residue R409 is an evolutionary conserved amino acid. The p.R409Q mutation, which is predicted as probably damaging, would alter the conformation of the protein slightly and would cause a decrease of gene expression. This is the first report of an EGR2 mutation presenting as an axonal CMT phenotype with variable severity. This study broadens the phenotype of the EGR2-related neuropathies and suggests that the genetic testing of patients suffering from axonal CMT should include the EGR2 gene.
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The high prevalence of patent foramen ovale in migraine with aura (MWA) seems to be well established; yet, the possible relation between the magnitude of the right-to-left shunt (RLS) and MWA is not so clear. As a hypothesis, if the RLS... more
The high prevalence of patent foramen ovale in migraine with aura (MWA) seems to be well established; yet, the possible relation between the magnitude of the right-to-left shunt (RLS) and MWA is not so clear. As a hypothesis, if the RLS played a precipitating role, subjects with a larger degree of shunt might experience a higher number of seizures. We examine this possible relationship between the magnitude of the shunt and the incidence of seizures. We examined a series of 72 patients with MWA to obtain the frequencies of seizures (dividing them into three groups of increasing frequency), history and precipitating factors. The presence and magnitude of the RLS were later determined by means of transcranial Doppler ultrasonography, following a method that had previously been validated. Univariate analysis was then used to evaluate the possible association between the magnitude of the shunt and the frequency of seizures. The mean age was 36 years. RLS appeared in 44 patients (61.1%) ...
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Hereditary neuropathy with abnormal liability to pressure palsies (HNPP) is a dominant autosomally transmitted disease that gives rise to foci of peripheral nerve myelination, reducing conduction and leading to episodes of palsy and... more
Hereditary neuropathy with abnormal liability to pressure palsies (HNPP) is a dominant autosomally transmitted disease that gives rise to foci of peripheral nerve myelination, reducing conduction and leading to episodes of palsy and sensory changes that are all linked to sensitivity to pressure and traction on the affected nerve roots. The molecular basis of HNPP has been identified as a submicroscopic deletion of the 17p11.2 chromosome in exactly the same region that it is duplicated in Charcot-Marie-Tooth disease, type 1A (CMT1A). We report genetic analyses of 13 patients (belonging to 3 families) diagnosed of HNPP by means of physical examination and electrophysiologic and morphologic tests (the last in 3 cases only). Inter- and intrafamilial variation in symptomatology was studied. Some patients presented the usual clinical signs, such as recidivating brachial plexus palsy, permanent sensory polyneuropathy, foot deformities and others that might also be found in patients with CM...
Research Interests: Humans, Female, Male, Electromyography, Pedigree, and 5 moreAged, Middle Aged, Adult, Peripheral nerves, and Chromosome Disorders
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... 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.
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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... more
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. 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, VAW412R3HEc and EW401HE...
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Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a pathogenic connection. The object of the study... more
Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a pathogenic connection. The object of the study is to investigate the prevalence of right-to-left shunt (RLS) in a cohort of patients suffering migraine with aura (MA) and its possible association with migraine attacks triggered by VPA. We investigated the circumstances triggering the migraine attacks, in a consecutive series of 72 MA patients and in a series of migraine without aura age and gender-matched. The presence and extent of RLS was assessed by transcranial Doppler. Massive RLS appeared in 38.9% of MA and in 6.5% of migraine without aura (p<0.001). MA patients identified at least one VPA as headache trigger in 45.8%. A trend was found between these triggering activities and massive RLS, both in MA group OR 2.7 [1.02-7.17] and in all migraine patients OR 2.5 [1.01-6.11]. According to ...
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To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy. A study conducted in the Safor region (Spain), setting of a large... more
To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy. A study conducted in the Safor region (Spain), setting of a large cluster of patients. Clinical, neurophysiologic, muscle imaging, and muscle biopsy studies and MYH7 gene sequencing were investigated in 32 patients from 4 kindreds. Data from 36 deceased or nonexamined patients were collected from hospital records or relatives. Onset ranged from congenital to the 6th decade. All patients presented weakness of great toe/ankle dorsiflexors and many had associated neck flexor, finger extensor, and mild facial weakness. In most cases, involvement of proximal and axial muscles was observed either clinically or by muscle imaging, sometimes giving rise to scapuloperoneal and limb-girdle syndromes. Disabling myalgias, skeletal deformities, and dilated cardiomyopathy in one patient were associated features. Life expectancy was not reduced but the spectrum of disability ranged from asymptomatic to wheelchair confined. Electromyographic neurogenic features were frequently recorded. Muscle fiber type disproportion, core/minicore lesions, and mitochondrial abnormalities were the most relevant pathologic alterations. All patients carried the p.K1729del mutation in MYH7. The p.K1729del mutation in the MYH7 gene expresses notable clinical variability and electromyographic and pathologic features that can lead to the misdiagnosis of neurogenic atrophies, congenital myopathies, or mitochondrial myopathies. Mutations in genes encoding other sarcomeric and reticulo-sarcoplasmic proteins involved in calcium regulation share pathologic characteristics with our patients, suggesting a possible pathogenetic connection.
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Epidemiological studies performed directly on the population show a prevalence of Friedreich&#39;s ataxia (FA) from 1 to 4.7 cases/100,000 inhabitants. An indirect epidemiological approach can be achieved using genetic methods like... more
Epidemiological studies performed directly on the population show a prevalence of Friedreich&#39;s ataxia (FA) from 1 to 4.7 cases/100,000 inhabitants. An indirect epidemiological approach can be achieved using genetic methods like consanguinity studies to determine the frequency of a mutated gene and the incidence of certain diseases in the population. We obtained consanguinity data of a series of FA patients in Valencia, Spain and the figures on consanguinity in the general population that were estimated according to the Archive of Dispensations given by the Catholic church for consanguineous marriages. From these data, the frequency of the FA gene was calculated as 1/127. From these data, applying the Hardy-Weinberg principle, the frequency of the carriers was 1/64 and the incidence was 6.18/100,000 live births. Assuming a life expectancy of FA of 45 years, the prevalence was 3.83/100,000 inhabitants. These figures are in the same range as those obtained in population studies.