Phenotypic correlations in a large single-center cohort of patients with BSCL2 nerve disorders: a clinical, neurophysiological and muscle magnetic resonance imaging study.

BACKGROUND AND PURPOSE: BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMNs). A series of BSCL2 patients is presented and clinical, neurophysiological and muscle magnetic resonance imaging (MRI) findings are correlated. METHODS: Twenty-six patients from five families carrying the p.N88S mutation were identified. Age of onset, clinical phenotype (dHMN, Charcot-Marie-Tooth, spastic paraplegia), physical examination, disability measured as a modified Rankin Scale score and neurophysiological findings were collected. A whole body muscle MRI had been performed in 18 patients. The pattern of muscle involvement on T1-weighted and short time inversion recovery sequences was analysed. Hierarchical analysis using heatmaps and an MRI Composite Score were generated. Statistical analysis was carried out with STATA SE v.15 (TX, USA). RESULTS: The mean age was 51.54 ± 19.94 years and 14 patients were men. dHMN was the most common phenotype (50%) and five patients (19.23%) showed no findings on examination. Disease onset was commonly in childhood and disability was low (modified Rankin Scale score 1.34 ± 1.13) although median time since onset of disease was 32 years (range 10-47). Charcot-Marie-Tooth-like patients were more disabled and disability correlated with age. On muscle MRI, thenar eminence, soleus and tibialis anterior were most frequently involved, irrespective of clinical phenotype. MRI Composite Score was strongly correlated with disability. CONCLUSION: Patients with the p.N88S BSCL2 gene mutation are phenotypically variable, although dHMN is most frequent and generally slowly progressive. Muscle MRI pattern is consistent regardless of phenotype and correlates with disease severity, probably serving as a reliable outcome measure for future clinical trials.

EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

PURPOSE: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

Melatonin in sleep disorders.

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.

Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1.

BACKGROUND: Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect. METHOD: We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders. RESULTS: Patients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence. CONCLUSIONS: Besides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.

Familial amyloidosis with polyneuropathy type 1 caused by transthyretin mutation Val50Met (Val30Met): 4 cases in a non-endemic area. / Polineuropatía amiloidótica familiar I por mutación Val50Met (Val30Met) en el gen de la transtiretina.

INTRODUCTION: Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) typically arises as an autonomic neuropathy primarily affecting small fibres and it occurs in adult patients in their second or third decades of life. It progresses rapidly and can lead to death in approximately 10 years. Other phenotypes have been described in non-endemic areas. OBJECTIVES AND METHODS: We described 4 cases from the Spanish province of Guipuzcoa, a non-endemic area, to highlight the clinical variability of this disease. PATIENTS AND RESULTS: Three patients presented a late-onset form manifesting after the age of 50, featuring a predominantly motor polyneuropathy initially causing distal impairment of the lower limbs followed by the upper limbs. One patient suffered severe neuropathic pain. None showed signs of autonomic involvement. The fourth patient, of Portuguese descent, presented a typical form with onset in her thirties, neuropathic pain and dysautonomia. All patients carry the Val50Met mutation in the TTR gene. CONCLUSION: FAP is a pleomorphic disease even in patients carrying the same mutation. In non-endemic areas, its main form of presentation may resemble a predominantly motor polyneuropathy developing in the sixth decade of life with no signs of dysautonomia. Given this non-specific presentation and the widely available technical means of studying the TTR gene, we believe that the protocol for the aetiological diagnosis of any polyneuropathy should include genetic sequencing of TTR.

Melatonin in sleep disorders. / Melatonina en los trastornos de sueño.

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.

Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy.

Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.

LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene.

We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene. The mean age at onset of LGMD2A patients was approximately 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, approximately 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG-->TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550DeltaA, G222R, IVS6-1G-->A, A483D, IVS17+1G-->T, 2069-2070DeltaAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less sensitive (52.5%) yet more specific (87.8%). In this case LGMD2I was a relevant cause of false-positive diagnoses. Considering both the clinical phenotype and the biochemical information together, the probability of correctly diagnosing a calpainopathy is very high (90.8%). However, if one of the analyses is lacking, the probability varies from 78.3 to 73.7% depending on the information available. When both tests are negative, the probability that the sample comes from a patient with LGMD2A was 12.2%.

Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: The FYDATA study.

BACKGROUND: Real-world data of current antiepileptic drugs (AEDs) used to treat focal seizures is of importance to understand the efficacy and safety outside of the clinical trial setting. Here we report real-world data from a large series of patients treated with perampanel for 1year. METHODS: FYDATA was a multicentre, retrospective, 1-year observational study assessing the efficacy and safety of adjuvant perampanel in patients ≥12 years of age with focal epilepsy in a real-world setting. At 12 months, the proportion of patients who were seizure free, median percentage seizure reduction, proportion of responders, retention rate and proportion of patients with adverse events (AEs) were assessed. Analyses were also performed to identify any patient-, medication- and disease-related factors associated with a large clinical response or carry a risk for AEs. RESULTS: A total of 464 patients were included in the study with a retention rate of 60.6% at 1year. The mean number of prior AEDs was 7.8. The median percentage reduction in overall seizures was 33.3% (75% for secondary generalised seizures) after 1year, with 7.2% of patients achieving seizure freedom. Furthermore, patients on non-enzyme-inducing AEDs were more likely to achieve seizure freedom, and logistic regression revealed that patients aged ≥65 years, those with epilepsy due to a vascular aetiology and those who had received fewer prior AEDs showed a better clinical response to perampanel. A total of 62.9% of the patients experienced AEs at 12 months; dizziness, somnolence and irritability were the most frequent AEs. Patients with prior psychiatric comorbidities (hyperactivity and personality disorder) were more likely to experience psychiatric AEs with perampanel, and slower titration schedules were associated with less AEs overall. CONCLUSION: Perampanel, for the treatment of focal epilepsy in a real-world setting in a refractory population, over 1year, demonstrates a similar efficacy and safety profile to that observed in clinical trials. Our results have implications for the optimisation of perampanel use in a clinical setting.

Identification and characterization of a novel human brain-specific gene, homologous to S. scrofa tmp83.5, in the chromosome 10q24 critical region for temporal lobe epilepsy and spastic paraplegia.

We describe the structure, genomic organization, and some transcription features of a human brain-specific gene previously localized to the genomic region involved in temporal lobe epilepsy and spastic paraplegia on chromosome 10q24. The gene, which consists of six exons disseminated over 16 kb of genomic DNA, is highly homologous to the porcine tmp83.5 gene and encodes a putative transmembrane protein of 141 amino acids. Unlike its porcine homolog, from which two mRNAs with different 5'-sequences are transcribed, the human gene apparently encodes three mRNA species with 3'-untranslated regions of different sizes. Mutation analysis of its coding sequence in families affected with temporal lobe epilepsy or spastic paraplegia linked to 10q24 do not support the involvement of this gene in either diseases.

Autosomal dominant nocturnal frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation in the CHRNA4 gene.

BACKGROUND: A large family with autosomal dominant nocturnal frontal lobe epilepsy from the south of Spain was studied. The clinical appearance of the disease in this family, which included 28 members, of whom 11 were affected and 2 were obligate carriers, was identical to that previously described in an Australian family and a Norwegian family, in which mutations in exon 5 of the CHRNA4 gene were found. METHODS: Following DNA extraction, the family was genotyped with 4 fluorescent markers flanking the locus to the CHRNA4 gene on chromosome 20q13.3, and lod score computations were performed. The exon 5 of the CHRNA4 gene was amplified between nucleotides 535 and 825 and polymerase chain reaction products were purified and sequenced directly. RESULTS: The same missense mutation as that found in the Australian family, C-->T, which causes the replacement of a serine with phenylalanine in amino acid 252 in exon 5, was detected. This mutation segregated with the disorder in all 11 affected members, in the 2 obligate carriers, and in 1 asymptomatic sibling, and was not found in 1 spouse and 1 daughter. Neither of the 2 polymorphisms found in a series of families with epilepsy were found in our sample [corrected]. CONCLUSIONS: These data confirm the clinical homogeneity in the phenotypic expression of autosomal dominant nocturnal frontal lobe epilepsy caused by mutation in the CHRNA4 gene, and the pathogenic role of the Ser252Phe mutation in this disorder.

Prevalence of myotonic dystrophy in Guipúzcoa (Basque Country, Spain).

Prevalence figures for inherited neuromuscular disorders are important both for health care planning purposes and for evaluating the need for DNA diagnostic services for eugenic approaches. We screened for the prevalence of myotonic dystrophy (MyD) through extensive inquiry of neurologic and primary health services of Guipúzcoa (Basque Country, northern Spain) between 1989 and 1991. Typical adult-onset and neonatal cases and relatives at risk; suffering from a partial syndrome, were included. In the latter, molecular typing was performed with DNA probes close to the MyD gene to demonstrate the MyD gene carrier status. The high prevalence detected (26.5 cases per 100,000 population) could be explained by methodological factors, but intrinsic factors, such as a possible founder genetic effect or the quick growth of the Guipúzcoa population since the last century may contribute to one of the highest MyD prevalence in the world. In the future, the methodological basis for epidemiologic surveys of MyD must combine molecular technology with more-extensive family inquiries.

Prevalence of Parkinson's disease and other types of Parkinsonism. A door-to-door survey in Bidasoa, Spain.

OBJECTIVES: To assess the prevalence of Parkinson's disease and parkinsonism in two Spanish populations (Irun and Hondarribia, Bidasoa Region) and to compare the results with those of similar surveys. METHODS: The survey included 2000 participants aged 65 years or older in a door-to-door, three-phase design. In the screening phase we used the SNES (Sicilian Neuro-Epidemiologic Study) screening questionnaire, which has 100% sensitivity. In phases 2 and 3 we carried out a 3-year follow-up of all cases diagnosed with parkinsonism in phase 2. Progressively stricter diagnostic criteria were chosen in order to minimize the impact of false positives on the final results. RESULTS: The prevalence of Parkinson's disease (PD) was 1.5 % (95% confidence interval, 0.9 to 2.3) and the prevalence of other types of parkinsonism (OP) was 1.1 % (95% confidence interval 0.6 to 1.9). The overall prevalence by age group was 0.4 % (65-74 years), 4.7% (75-84 years), and 2.9% (> or =85 years) for Parkinson's disease and 0.7%, 2%, and 3.9 % for parkinsonism, respectively. The other parkinsonism prevalence was 1.3 % in men and 1.6 % in women. CONCLUSIONS: These prevalence rates are similar than those found in studies made in other European countries. The prevalence of both Parkinson's disease and other types of parkinsonism increased with age, with no significant differences between men and women.

Tardive akathisia due to sulpiride.

A 56 year-old woman who suffered from parkinsonism, oro-lingual dyskinesia (OLD) and tardive akathisia (TA) due to sulpiride is reported. OLD and TA appeared after sulpiride withdrawal. The patient was successfully treated with tetrabenazine even a mild parkinsonism was present. TA seems to be related with an apparent dopaminergic hyperactivity and it has to be differentiated of other neuroleptic-induced movement disorders such as restless legs syndrome in order of an appropriate treatment. Sulpiride has the same possible side effects than classic neuroleptics.

Adaptation of the lumbar spine to different positions in bicycle racing.

STUDY DESIGN: A radiologic and electromyographic study was done of the adaptation of the lumbar spine to high-performance cycling. OBJECTIVES: To evaluate changes in the lumbar spine produced by different cycling positions on different types of bicycles used during competition. METHODS: Three professional cyclists were observed to evaluate changes in the lumbar spine. Radiographs were obtained of the different positions adopted by the cyclists during competition, and changes in the angles of the lumbar spine were measured. An electromyographic study was done of the abdominal, lumbar, and thoracic paravertebral muscles. RESULTS: The cyclists' positions involved a change from discal lordosis to kyphosis. To obtain a more aerodynamic position, the cyclists flexed the hip and made the pelvis horizontal without changing disc angles. The contraction of paravertebral lumbar muscles was proportional to pedalling intensity and decreased in more aerodynamic positions. The tone of the paravertebral thoracic muscles depended on the extent of cervical hyperextension. Abdominal muscles remained relaxed in all bicycle positions and with all pedalling intensities. CONCLUSIONS: The changes observed could modify the normal biomechanics of the lumbar spine, but the overall mechanical load on the spine is reduced by shifting weight onto the upper limbs. The imbalance that occurs between the activity of flexor and extensor muscles could cause lumbar pain in persons without proper physical preparation.

[Clinical manifestations of myotonic dystrophy: epidemiologic survey]. / Manifestaciones clínicas de la distrofia miotónica: encuesta epidemiológica.

BACKGROUND: The presence of a local aggregation of cases of myotonic dystrophy (MD) allows the evaluation of clinical symptoms of the disease in a sample in which the influence of a possible genetic heterogeneity is decreased. METHODS: The degree of global neuromuscular handicap and the incidence and severity of four of the most characteristic symptoms (cataracts, myotonia, muscular weakness and neuropsycologic disturbances) were studied in 183 patients with MD (146 typical adult forms, 19 neonatal, and 18 partial syndromes) in relation with the age of onset of the symptomatology or length of disease. RESULTS: Only 8.3% of the patients (excluding the neonatal forms) were severely handicapped, and the degree of neuromuscular handicap depended fundamentally on the age of onset of the disease. Cataracts and myotonia were present in 87 and 89% of the patients, respectively. Almost all the patients above the age of 40 presented cataracts. No clinical or subclinical evidence of neuromuscular involvement was present in 11% of the patients with MD. These patients principally corresponded to the group in whom the disease initiated over the age of 50. CONCLUSIONS: The age of onset of the symptomatology appears to be the determining factor to establish both the global prognosis of neuromuscular incapacity of patients with myotonic dystrophy and the explanation of the chronology of the appearance of the most characteristic symptoms of the disease. The presence of carriers without neuromuscular symptomatology is of note, this fact reinforcing the need to incorporate DNA examination in the evaluation of asymptomatic relatives or with exclusive ocular symptomatology.

[Muscular dystrophy due to a mutation in the gene of alpha-sarcoglycan subunit of dystrophin associated protein complex]. / Distrofia muscular por déficit de la subunidad alfa-sarcoglucano del complejo de proteínas relacionadas con la distrofina.

Linkage studies have confirmed the existence of clinical an genetic heterogeneity among the muscular dystrophies due to adhalin deficiency. We present the clinical, histological and genetic characteristics in a case of primary adhalinopathy (deficiency of the 50 kD subunit or alpha-sarcoglycan). It was a 19 years-old woman, born of non consanguineous parents, who shows a long evolution myopathy with onset before age 7, a severe evolution and becoming wheelchair bound at 10 years. She showed evident calf pseudohypertrophy and serum creatinkinase (CK) levels were elevated (40-180 times the standard level). The histological pattern showed a destructed fascicular architecture in agreement with severe muscular dystrophy, normal staining with anti-dystrophin monoclonal antibodies and abnormal staining pattern with anti-adhalin antibodies. The molecular study evidenced an homozygous point mutation (Arg-->Cys) at position 77 of exon 3 of the gene coding for the 50 kD subunit of the alpha-sarcoglycan complex localised in chromosome 17. In the light of this case, we suggest a revision of the diagnostic orientation in the muscular dystrophies and we review the new taxonomy of the limb-girdle muscular dystrophies, remarking the clinical signs which could indicate a given genetic locus.

Drugs inducing or aggravating parkinsonism: a review.

Drug-induced parkinsonism (DIP) is frequent. The list of drugs able to induce parkinsonism is long and probably incomplete, because new drugs, with previously unknown antidopaminergic activity, are constantly being added. Not all the drugs have the same potency for inducing parkinsonism. We classify these drugs in three groups: (1) drugs with obvious antidopaminergic activity which regularly induce parkinsonism; (2) drugs able to induce parkinsonism in particular individuals and (3) drugs which may aggravate Parkinson's disease treated with levodopa. The reports of isolated cases of parkinsonism induced by widely-used drugs (drugs in group 2) may be the result of either an idiosyncratic side effect or a misdiagnosis of parkinsonism. The antidopaminergic activity of the drugs of this group is weak and not sufficiently demonstrated. Maybe, in these cases, the blockage of other neurotransmitters different from dopamine plays a role in the induction of parkinsonism. Probably, the number of patients with DIP is higher than reported or detected, because many patients suffer from weak symptoms that quickly disappear after drug withdrawal. One of the main points of interest is knowing the list, because all these drugs, specially those of group 1, should be avoided or used with caution in the treatment of some common symptomatic problems in patients with Parkinson's disease, such as depression, arterial hypertension, diabetes mellitus and cardiac disorders. The precautions should extent to other populations especially susceptible to suffer from DIP, such as the elderly or patients with other neurodegenerative disorders, such as Alzheimer's disease.

[Neuropathy associated with arteriosclerosis]. / Neuropatía asociada a arteriosclerosis.

OBJECTIVE: To determine the frequency and characteristics of the neuropathy associated with arteriosclerosis. MATERIAL AND METHODS: A prospective clinical and electrophysiological study was made of 29 male patients with arteriosclerosis, in whom other causes of polyneuropathy had been excluded. RESULTS: Eleven patients complained of paresthesiae (mostly mild). In 11 patients there were signs of polyneuropathy on clinical examination. Neurophysiological studies were abnormal in 11 patients, suggesting the presence of predominantly sensitive axonal neuropathy. In five patients with paresthesiae both physical examination and electrophysiological studies were normal. In 17 patients there were changes in the somatosensory evoked potentials. The brainstem auditory evoked potentials of 27 patients were suggestive of diffuse changes in central nervous conduction, together with super-imposed focal lesions. There were no differences as regards age, signs of disease in the legs or of the involvement of widespread illness, whether they were smokers, ex-smokers or non-smokers, the number of cigarettes smoked daily or the total duration of the smoking habit between the patients with and without clinical or electrophysiological polyneuropathy. CONCLUSIONS: Approximately one third of the patients with arteriosclerosis have clinical or electrophysiological signs suggestive of predominantly sensitive axonal polyneuropathy. In some cases the patients had paresthesia but no changes were seen on physical or electrophysiological examination. The evoked potentials showed diffuse changes in central nervous conduction, and in some cases this was associated with signs of focal lesions.

[Alterations in functional proteins. Calpaine-3 deficiency]. / Alteraciones en las proteínas funcionales. Déficit de calpaína 3.

INTRODUCTION: Muscular dystrophies due to calpain deficiency are the first example of a muscular dystrophy due to the mutation of a gene codifying for a non-structural enzymatic protein of unknown function and substrate. DEVELOPMENT: More than 70 mutations have been described in the gene structure, localized to chromosome 15. Although the time course and topography is fairly homogeneous, correlation between the different mutations and the phenotype has still to be analyzed. The age of onset of symptoms is usually between 8 and 14, with no difference between the sexes. There is a slow but uniformly progressive course starting in the pelvis and extending to the shoulder and the distal musculature. Almost all patients are confined to a wheelchair twenty years after onset of the disease. There is no facial, oculomotor or bulbar involvement and gemellar pseudohypertrophy is rare. However, a winged scapula and marked lumbar hyperlordosis is universal. No cardiac or cognitive changes have been observed. Muscle CT shows a pattern of atrophy, mainly of the posterior and medial muscle compartments and of the posterosuperficial group of the legs, which varies depending on the time the disorder has been present. This condition is the commonest etiological group of the dystrophy syndromes, especially of those of late infancy or juvenile onset, in the open populations studied to date. Muscle biopsy, stained by all methods available, is essential to rule out other types of progressive dystrophies secondary to deficiencies of structural proteins.