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Introduction: Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations., Patients and Methods: Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions., Results: We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P < .01), with a higher proportion of women in this group (P < .01). Disease severity at diagnosis and at the time of data analysis was higher among patients with refractory MG, who presented more relapses during follow-up. Logistic regression analysis revealed an independent association between refractory MG and the number of severe relapses., Conclusions: The percentage of patients with refractory MG in our series (13%) is similar to those reported in previous studies; these patients were often women and presented early onset, severe forms of onset, and repeated relapses requiring hospital admission during follow-up., (Copyright © 2020 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Ocular myasthenia gravis (MG) is the most common phenotype of MG at onset. A variable percentage of these patients develop secondary generalisation; the risk factors for conversion and the protective effect of immunosuppressive treatment are currently controversial., Patients and Methods: We designed a retrospective single-centre study with the aim of describing the demographic, clinical, and laboratory characteristics of a Spanish cohort of patients with ocular MG from Hospital Universitario de Albacete from January 2008 to February 2020., Results: We selected 62 patients with ocular MG from a cohort of 91 patients with MG (68.1%). Median age at diagnosis was 68 (IQR, 52-75.3), and men accounted for 61.3% of the sample (n = 38). Most patients presented very late-onset ocular MG (n = 34, 54.8%). Binocular diplopia was the most frequent initial symptom (51.7%). The rate of progression to generalised MG was 50% (n = 31), with a median time of 6 months (IQR, 2-12.8). Female sex (OR: 5.46; 95% CI, 1.16-25-74; P= .03) and anti-acetylcholine receptor antibodies (OR: 8.86; 95% CI, 1.15-68.41; P = .04) were significantly associated with the risk of developing generalised MG., Conclusions: The conversion rate observed in our series is relatively high. Generalisation of MG mainly occurs during the first 2 years of progression, and is strongly associated with female sex and especially with the presence of anti-acetylcholine receptor antibodies., (Copyright © 2020 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Ulnar mononeuropathy at the elbow is the second most frequent neuropathy in humans. Diagnosis is based on clinical and electrophysiological criteria and, more recently, also on ultrasound. Cross-sectional ultrasound is currently the most valued, although longitudinal ultrasound allows assessment of the entire affected trajectory of the nerve in a single view, but always in a straight line with no changes in direction, as in the extended elbow. The main aim of this work is to propose normative values ​​for longitudinal ultrasound of the ulnar nerve at the elbow., Methods: The neurological exploration of upper extremity, and electrophysiological and ultrasound parameters at the elbow of ulnar nerve were evaluated in 76 limbs from 38 asymptomatic subjects., Results: The diameters of the nerve as well as the distal and proximal areas were larger at the proximal region of the ulnar groove, and even more so in older individuals. In most of these elderly subjects, we found a small, non-significant slowdown in motor conduction velocity at the elbow with respect to the forearm (less than 5 m/s)., Conclusions: We observed a good correlation between the longitudinal and cross-sectional ultrasounds of the ulnar nerve at the elbow. Longitudinal ultrasound proved to be sensitive, reliable, simple and rapid, but its greatest contribution was allowing the visualization of the entire nerve trajectory in an integrated way, providing an image with good definition of the outline, proportions and intraneural characteristics of the nerve., (© 2023. The Author(s).)

Introduction: Ocular myasthenia gravis (MG) is the most common phenotype of MG at onset. A variable percentage of these patients develop secondary generalisation; the risk factors for conversion and the protective effect of immunosuppressive treatment are currently controversial., Patients and Methods: We designed a retrospective single-centre study with the aim of describing the demographic, clinical, and laboratory characteristics of a Spanish cohort of patients with ocular MG from Hospital Universitario de Albacete from January 2008 to February 2020., Results: We selected 62 patients with ocular MG from a cohort of 91 patients with MG (68.1%). Median age at diagnosis was 68 (IQR, 52-75.3), and men accounted for 61.3% of the sample (n = 38). Most patients presented very late-onset ocular MG (n = 34, 54.8%). Binocular diplopia was the most frequent initial symptom (51.7%). The rate of progression to generalised MG was 50% (n = 31), with a median time of 6 months (IQR, 2-12.8). Female sex (OR: 5.46; 95% CI, 1.16-25-74; p = .03) and anti-acetylcholine receptor antibodies (OR: 8.86; 95% CI, 1.15-68.41; p = .04) were significantly associated with the risk of developing generalised MG., Conclusions: The conversion rate observed in our series is relatively high. Generalisation of MG mainly occurs during the first 2 years of progression, and is strongly associated with female sex and especially with the presence of anti-acetylcholine receptor antibodies., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations., Patients and Methods: Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions., Results: We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P<.01), with a higher proportion of women in this group (P<.01). Disease severity at diagnosis and at the time of data analysis was higher among patients with refractory MG, who presented more relapses during follow-up. Logistic regression analysis revealed an independent association between refractory MG and the number of severe relapses., Conclusions: The percentage of patients with refractory MG in our series (13%) is similar to those reported in previous studies; these patients were often women and presented early onset, severe forms of onset, and repeated relapses requiring hospital admission during follow-up., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

In surgical procedures of the supraclavicular and lateral cervical regions, as well as in cardiac and mediastinal surgeries, diaphragm function can be compromised by the risk of injury to the phrenic nerve and/or the C4 root. There are few publications that treat the intraoperative stimulation of these nerve structures to evaluate their functionality and, to our knowledge, until now it has not been hypothesized about whether it is possible to reduce the injury rates, which reach 26% in some cardiac surgery studies. We describe the technique used for the neurophysiological monitoring of the phrenic nerve. Also, its usefulness and advantages over other techniques are discussed. We conclude that, with the increasing incorporation in recent years of intraoperative neurophysiological monitoring, its application to the phrenic nerve is possible in procedures with a risk of injury and, thus, the reduction of iatrogenic injury rates may be feasible., (Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

Congenital myasthenic syndromes are a group of genetically determined rare diseases resulting from ultrastructural alterations in synaptic proteins. Up to 32 genes are known to be involved in those syndromes and many mutations have been reported, of which less than 8% affect the presynaptic complex. One of these syndromes is caused by the impairment of the presynaptic sodium-dependent high-affinity choline transporter 1, as a result of a mutation of the SCL5A7 gene associated with congenital myasthenic syndrome type 20 (MIM # 617143). We present a new case of this syndrome, caused by a mutation not previously described. A full term infant presented with acute respiratory failure and generalized weakness. The genetic analysis revealed the patient to be compound heterozygous for a new mutation of the SCL5A7 gene. The genetic analysis of congenital myasthenic syndromes provide information on the ultrastructural underlying mechanisms, which is valuable for differential diagnosis and specific treatments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Brivaracetam is currently indicated as adjunctive therapy for patients with focal-onset seizures with or without secondary generalization. However, it has been suggested that it could provide broad-spectrum efficacy given its similarity to levetiracetam and based on the results from preclinical studies and others of patients with generalized epilepsy. We present the case of a woman with refractory idiopathic generalized epilepsy and absence seizures with dramatic response to brivaracetam. Our report supports a consideration of treatment with this new antiepileptic drug on a case-by-case basis in patients with refractory generalized epilepsy, while we await further studies on this topic.

Antiepileptic drugs may occasionally increase seizure frequency or eliciting de novo seizure occurrence; the underlying mechanism of these effects is not known. The potential adverse effects of valproic acid in myoclonic astatic epilepsy have been noted by experienced clinicians in various different regions of the world, but this important observation has not been sufficiently reported. We present the case of tonic status epilepticus in an 8-year-old boy with Doose syndrome related to valproic acid. Valproic acid, such as others antiepileptic drugs, is liable to produce paradoxical effects such as the atypical seizures we report. We emphasize the importance for the management of acute seizures in an intensive care unit setting and increase awareness of the acute toxic effects of antiepileptic drugs., (Georg Thieme Verlag KG Stuttgart · New York.)

Spinal muscular atrophy and progressive myoclonic epilepsy (SMAPME, OMIM#159950) is a rare autosomal recessive disorder characterized by the combination of progressive myoclonic epilepsy and muscular weakness due to lower motor neuron disease. Mutations in ASAH1, previously associated only to Farber disease, have been recently described in seven patients with SMAPME. A homozygous c.125C>T mutation was initially found in six patients with a clinical homogeneous phenotype. A heterozygous compound mutation found in an additional patient has broadened the clinical and genetic spectrum of clinical SMAPME. We report a new case of a 13-year-old girl with SMAPME with the homozygous ASAH1 c.125C>T mutation, unique in that it is due to paternal uniparental disomy. She experienced muscle weakness from the age of three due to lower motor neuron involvement that lead to severe handicap and onset in late childhood of a progressive myoclonic epilepsy. This clinical picture fully overlaps with that of previously reported patients with this mutation and supports our view that the clinical phenotype associated with the homozygous c.125C>T mutation constitutes a clinically homogenous and recognizable disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Morton's neuroma causes metatarsalgia due to the interdigital neuropathy. The small nerve diameter compromises their evaluation in image studies. To overcome this problem we propose a new electrophysiological test., Methods: We conducted a prospective case-control study performing a orthodromic electroneurography using subdermal electrodes in controls and patients to assess the validity. Additionally all patients were tested with magnetic resonance. Some patients required surgery and subsequent histological evaluation., Results: The new ENG procedure showed higher sensitivity and specificity. Methodological standardization was easy and the test was well tolerated by the subjects., Conclusions: Our test demonstrated remarkable diagnostic efficiency, and also was able to identify symptomatic patients undetected by magnetic resonance, which underlines the lack of correlation between the size and intensity of the lesion. This new electrophysiological method appears to be a highly sensitivity, well-tolerated, simple and low-cost for Morton's neuroma diagnosis., (Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

The study was performed to characterize GASH:SAL audiogenic seizures as true epileptic activity based on electroencephalographic markers acquired with a wireless implanted radiotelemetry system. We analyzed cortical EEG patterns synchronized with video recordings of convulsive behavior of the GASH:Sal hamster following an acoustic stimulus. All GASH:Sal presented archetypal motor symptoms comparable to current animal models of generalized tonic-clonic epilepsy. Seizures consisted of an initial bout of wild running, followed by opisthotonus, tonic-clonic convulsions, tonic limb extension, and terminated in postictal depression. EEG patterns correlated with behavior and displayed phase appropriate spike-wave complexes, low-amplitude desynchronized activity, and high frequency large-amplitude peaks. Our results confirm that electroencephalographic profiles of the audiogenic seizures of the hamster GASH:Sal are parallel to EEG patterns of other animal models of generalized tonic-clonic seizures. Therefore, this animal may serve as an appropriate model for epilepsy research., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We present a girl with the characteristic clinical picture associated with Marden-Walker syndrome (MWS; OMIM 248700), including mask-like face with blepharophimosis, joint contractures, intellectual disability, a multicystic dysplastic kidney and cerebral dysgenesis. The long-term follow-up allowed us to monitor the evolution of the phenotype in this patient, and among the main findings we highlight the following: demyelination of the pyramidal tract demonstrated by transcranial magnetic stimulation and the involvement of the levator muscles of angle of mouth in fixed facial expression with relative integrity of the rest of the facial expression muscles. A 244 k array comparative genomic hybridization (aCGH) was carried out and showed a de novo interstitial deletion of approximately 2.84 Mb affecting only the cytoband 21q22.11 (genome coordinates chr21:31,874,016-34,711,763). We selected 10 of the most recent published cases with either total or partial deletions of cytoband 21q22.11 that provided good characterization of the genomic size or the genes in the deleted regions. We observed that in nine of the 10 cases the deleted regions included the RUNX1 gene in 21q22.12, which is not affected in the current patient's deletion or in that of Patient 3 from Roberson et al. [2011]. After a comparison of shared deleted genes between cases, and correlation of their potential phenotypes, we concluded that the pattern of defects considered for a diagnosis of MWS may represent part of the phenotypic expression of a partial or total deletion of 21q22.11., (Copyright © 2013 Wiley Periodicals, Inc.)

Introduction: Blinking is usually a spontaneous movement that takes place as a consequence of the alternating and antagonistic activity of the orbicularis oculi and levator palpebrae superioris muscles. In order to achieve an efficient movement, they are regulated by a reciprocal inhibition in such a way that the agonistic movement triggers the simultaneous inhibition of the antagonist, and vice-versa. Co-contraction is the dysfunction of this mechanism and is a significant phenomenon in dystonic disorders, especially in simple movements that are not subject to variability, as is the case of blinking. Blepharospasm is the most frequent dystonia affecting adults and it is easy to diagnose. In incipient processes it may offer some difficulties and can even be mistaken for other processes. We evaluate the possibility of an early diagnosis of blepharospasm in patients with palpebral hyperfunction with a short time to progression., Patients and Methods: A prospective evaluation of 23 patients with suspected blepharospasm was conducted. Each of them was submitted to a simultaneous electromyographic study of the orbicularis oculi and levator palpebrae muscles., Results: The presence of co-contraction in any of the blinking movements recorded was related with the chances of developing blepharospasm in the following years. None of the patients who did not have dystonic blinking presented blepharospasm in the years of the follow-up; in contrast, it was developed by all of those who presented it on some occasion., Conclusions: Dystonic blinking was observed in all the patients with blepharospasm, and blinking was physiological in those who did not present it. Simultaneous electromyographic evaluation of the muscles of the eyelids is a simple, sensitive, well-tolerated and particularly specific examination that can be used to determine whether a patient will show blepharospasm in an early stage of development.

Pneumococcal meningoencephalitis (PME) is a life-threatening condition of the central nervous system (CNS), and is often the result of a complicated upper airway infection. Periodic Lateralized Epileptiform Discharges (PLEDs) are a typical electroencephalographic (EEG) pattern found in some acutely acquired brain insults. Within the pediatric population they are frequently seen in association with herpetic encephalitis, a CNS infection with a high morbidity and mortality rate. We report the case of a 3-year-old girl with a bilateral ear infection who developed convulsions and coma. She had early PLEDs lateralized to the right on the EEG and microbiological criteria for Streptococcus pneumoniae infection. Concomitant herpetic encephalitis was ruled out. Intensive antibiotic and antiepileptic treatment resulted in a remarkable improvement, with the patient being able to resume her normal activities within months. To our knowledge, the association of PME and PLEDs has not been previously described in children. On the other hand, EEG has scarcely been used in the management of acute CNS infections. Hence, non-herpetic CNS encephalitis with potentially more favorable outcomes ought to be considered in the differential diagnosis of PLEDs. Continuous EEG monitoring should be considered in children with CNS infections presenting with altered sensorium, independent of the presence of seizures., (Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Aims: Nitric oxide (NO) is synthesized from L-arginine (L-Arg) by three different isoforms of NO synthase (NOS), i.e. the constitutive neuronal and endothelial NOS (nNOS and eNOS) and the inducible NOS (iNOS). NO has been involved in the pathophysiology of epilepsy, but available data are conflicting and the actual role of NO in epilepsy still remains to be clarified. In this study we investigated the basal and post-seizure levels of constitutive NOS (cNOS) activity as well as the expression of the cNOS isoforms across brain regions in a novel model of epilepsy., Main Methods: cNOS activity was assessed in various brain areas along the rostro-caudal axis in control wild type hamsters, unstimulated generalized audiogenic seizure prone hamsters, Salamanca strain, GASH:Sal and GASH:Sal after 10 sound-induced epileptic seizures. Additionally, Western blot experiments for nNOS and eNOS were performed in those areas where relevant changes in cNOS activity were found., Key Findings: In the GASH:Sal, cNOS activity increased in the mesencephalic areas studied while cNOS activity decreased in both the striatum and cerebral cortex after 10 sound-induced epileptic seizures. nNOS (but not eNOS) expression paralleled the variations in cNOS activity. The same sound stimulation had no effect on control hamsters., Significance: These results suggest a different NOS response in the regions close to the original epileptic focus (caudal, in our auditory model) versus the remote areas (rostral) possibly recruited at later stages or after repeated crises. These findings may account for some of the discrepancies found regarding the role of NO in epilepsy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Nerve anastomoses in the hand are deviations from the anatomical norm. They do not lead to illness, but still they are events related with electrodiagnostic difficulties and, due to their unexpected presentation, also with iatrogenesis in regional surgical interventions., Case Report: We report the neurophysiological study conducted on a 45-year-old female who was found to have Riche-Cannieu-type motor anastomosis between the median and ulnar branches in the palm of the hand, complete innervation of the 4th finger by the ulnar nerve and complete innervation by the superficial radial of the back of the hand., Conclusions: Anatomical descriptions of abnormal innervations in the hand are frequent, especially of the sensory kind. They do not usually give rise to any problems, even when the communicating branch is injured, probably owing to the scant participation of axons that usually occurs in anastomosis. They are not difficult to recognise by means of electroneurography if we are aware of their different types and we have a good knowledge of the anatomical routes. This will enable us to develop accurate diagnostic protocols. Knowledge of these variants will prevent electrodiagnostic errors and surgical iatrogenic effects from occurring.

Satoyoshi syndrome is a rare disease presumed to be immunologically mediated, characterized by muscle spasms, alopecia and diarrhea. We describe the case of a female in whom the muscle spasms were the predominant feature and we analyze the changes in cortical and in spinal excitability under the paired pulses paradigm. Hyperexcitability was present in the H-reflex study, thus suggesting that the spinal cord is the structure most likely responsible for the spasms. This is the first reported case in Spain., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Hypereosinophilic syndrome is produced by what is usually a multiple infiltration of eosinophils into tissues, and may be secondary or idiopathic, depending on whether it is related to a specific aetiology or not. It is not uncommon for it to include nerve disease, but it is unusual for it to do so in the form of multineuritis. Exceptionally, pathogenesis into multiple mononeuritis appears to be related with neurotoxicity due to products derived from eosinophils rather than with infiltrating or inflammatory phenomena. This study describes the case of a female patient with hypereosinophilic syndrome with no verifiable cause, multineuritis and eosinophilic fasciitis., Case Report: A 30-year-old female with no relevant history who visited because of some painless inguinal nodules that had appeared several weeks before. At almost the same time, she presented painful sensitive symptoms in her legs with a significant functional incapacity. An important degree of hypereosinophilia, eosinophilic fasciitis and non-neoplastic eosinophilic infiltration of the bone marrow was found, together with multiple mononeuritis. Treatment with oral corticoids improved the dermatological and haematological clinical features, and associating it with gabapentin improved the neuropathic symptoms., Conclusions: The patient, in accordance with current criteria, presented idiopathic hypereosinophilic syndrome with an undetermined subtype. To our knowledge, the association with eosinophilic fasciitis and multineuritis has not been reported to date. There is no proven infiltrating mechanism in multiple mononeuritis, which corroborates the poor control of the neuropathic clinical symptoms with oral corticoid therapy. Association with gabapentin, which stabilises the axonal membrane, also backs up the neurotoxic pathogenetic hypothesis.

Periodic Lateralized Epileptiform Discharges (PLEDs) are usually seen in the context of destructive structural lesions of the cortex, more frequently in acute ischemic stroke and less common in tumours and meningoencephalitis, specially herpes simplex virus. Its origin and prognosis are uncertain but it is known that PLEDs are linked to epilectic seizures, including status epilepticus.We report on a 75-year old woman with pneumococcal meningoencephalitis who presented altered level of consciousness, acute focal deficits, convulsive seizures and PLEDs in left hemisphere. The finding of PLEDs on the electroencephalogram is related to focal lesions of heterogeneous origin, which up to date, have not been documented in pneumococcal infections of the central nervous system. Our case highlights the importance of identifying and addressing any modifiable etiologic factors of PLEDs.

The palmar cutaneous branch of the median nerve is highly exposed to trauma at the wrist; nevertheless, very few cases have been reported. We report four cases of this neuropathy, three being superficial while the fourth was deeper or more severe. The neuropathy was confirmed using electro-neurophysiological assessments. Macroscopically, the nerve appeared compressed and enlarged, and in all cases, surgical repair produced a significant improvement. This neuropathy often follows minor traumas and, maybe, should be taken into account as part of the differential diagnosis of posttraumatic or postsurgical lateral and distal wrist pain.

Introduction: Metatarsalgia is the main symptom of a group of frequent ailments characterised by pain in the balls of the feet. Clinical knowledge and the availability of efficient complementary examinations are useful tools for the neurologist., Aim: To describe the range of processes related with metatarsalgia and a basic diagnostic schema that allows the aetiology to be differentiated., Development: We perform an elementary review of the neurological anatomy of the foot and outline the different neuropathies affecting the region, as well as the extra neurological processes that could call for a differential diagnosis., Conclusions: Familiarity with the pathologies responsible for metatarsalgias, whether they are neurological or not, is an enriching element for the diagnosis and management of these patients, as well as for greater efficiency in the referral among the medical professionals involved.

Peripheral Facial palsy (PFP) is generally considered a benign condition with good recovery and no sequelae. Yet, a distortion in the gesture and abnormal blinking, as those typically found in blepharospasm, can potentially develop early on. Such abnormal movements seem to be related to remodelling mechanisms that take place in the process of recovery. We report 2 cases where such clinical features became evident following an idiopathic PFP, as a result of reciprocal inhibition of orbicularis oculi and levator palpebrae. Hence, the neurophysiological study revealed an increased frequency in the blinking, with bilateral trigeminal-facial facilitation and, most notably, a disturbance that only became evident when the eyes were maintained wide open. Interestingly, those features were not reproduced in other tasks where the blinking conditions had not been altered. Our findings suggest that sensory inputs (reflex afferent pathways) are involved in such abnormal movements. The insufficient eyelid closure (lagophthalmus) in the context of PFP is likely to account for the exaggerated corneal vulnerability, thus resulting in abnormal mechanisms of adaptation.

We present the clinical course and EEG evolution of an extreme low birth weight preterm neonate with an uncommon type of glycine encephalopathy. The patient presented with myoclonic jerks, apnea and encephalopathy three months after birth without satisfactory therapeutic response. During the first days of clinical symptoms the patient presented a paroxystic burst-attenuation EEG pattern which progressively evolved into an established typical burst-suppression pattern within a few days. West syndrome occurred four weeks later and the patient died at seven months of extra-uterine life due to a serious respiratory infection with cardio-respiratory arrest. Genetic analysis showed a non-previously described mutation affecting a consensus splice site (IVS2-1G > C 3) in the AMT gene encoding the T protein of the glycine cleavage system.

Mutations in C-terminal titin cause autosomal dominant tibial muscular dystrophy (TMD) as reported previously. Samples from 25 new families and 25 sporadic new distal myopathy cases were screened for titin mutations. Three novel mutations were discovered in two families from Spain and two families from France. Two mutations, g.292998delT and g.293376delA lead to frameshift and premature stop codons in the second last and the last titin gene (TTN) exons, Mex5 and Mex6, respectively. The third was a nonsense mutation g.293379C>T (p.Q33396X) in Mex6. Patients with the upstream Mex5 mutation showed a more severe phenotype with earlier onset implying a genotype-phenotype correlation.

The term polyneuropathy (PNP) is used to describe a group of entities affecting the peripheral nerves, due to external trauma or internal pathology. The prevalence of PNP in the elderly is between 5 and 10%. Despite the multiplicity of causes, the most common etiological factor is diabetes. PNP is characterized by a wide variety of symptoms, due to the multiple functions of nerves. Clinical manifestations range from sensory or motor deficit to inability to maintain gait and stability. Diagnosis is difficult in the elderly, and can be a challenge to the geriatrician in patients with functional impairment. The gold standard for diagnosis is electrophysiology testing. The present article describes the main PNP in the elderly based on the physiopathology of these diseases and provides a practical proposal for clinical classification.

Introduction: Leprosy is a widespread infectious disease in humans that is endemic to regions with poor sanitary conditions, especially in cases of overcrowding, malnutrition and bad hygiene. The disease is characterised by dermopathy, which is quite typical, but above all by neuropathy, which often becomes the most important element. In most cases, alterations to nerves are defined by sensory deficits that are predominantly distal and multiple neuritis in areas where nerve entrapment has taken place., Case Reports: Two patients, both native Spaniards, presented largely overlapping clinical pictures, that is, a history of 'glove and stocking' type paresthesias and dysesthesias going back months or even years and functional impotence, which gave rise to a very pronounced gait disorder. In the two cases, the immunological situation was determined to be borderline lepromatous leprosy. The neurophysiological study revealed the presence of severe, diffuse sensory-motor axonal polyneuropathy that was predominantly distal, and several entrapped nerves. The dermatological illness was greatly improved by the treatment. The same was partially true, although to a satisfactory extent, of the neurological disease., Conclusion: We describe the cases of two Spaniards with borderline lepromatous leprosy with no past history of the disease, in whom neuropathy was the predominant symptom. We highlight the speed with which the neuropathies progressed, probably due to a change in 'polarity', and the severity of the neurological deficits in comparison with the dermopathy, in an unusual immunological situation. The growing number of native patients in the first world, even when there is no relevant history, suggests that we should not think of leprosy as something only occurring in immigrant patients from places where it is endemic, although the epidemiological relationship has still not been determined.

Introduction: Hirschsprung's disease (HD), or aganglionic megacolon, is a congenital disorder that is characterised by the absence of ganglion cells in the submucosal and myenteric plexuses of the intestine, which is caused by the failure of these cells to migrate from the neural crest (neurocristopathy). Cerebral dysgenesis and polymalformation syndromes have been reported in association with HD, thus suggesting an abnormal morphogenesis., Aim: To study the frequency of cerebral malformations in patients with HD in our environment., Patients and Methods: We conducted a retrospective study of 41,666 live newborn infants, over the period 1993-2003, and 17 cases of HD where identified., Results: The incidence of HD in the health district of the province of Albacete is 1.68 per 5,000 live newborn infants. Of the 17 patients with HD who were studied, 10 were isolated (58.8%) and seven (41.1%) were associated to other structural abnormalities and psychomotor retardation. Three of the cases in this latter group were due to chromosome pathology (trisomy 21, Down syndrome), two were caused by specific polymalformation syndromes (one Mowat-Wilson syndrome and one possible FG syndrome), one was due to a pattern of abnormalities that did not fit any known syndrome, and one had a normal phenotype and isolated cerebral dysgenesis. In all of cases the neuroimaging studies identified cerebral dysgenesis that was compatible with neuronal migration disorders., Conclusions: The frequency of association of HD, either isolated or within the context of a specific malformation syndrome, with neuronal migration disorders is high (23.5%). We suggest a full genetic and neurological evaluation should be carried out in patients with HD, together with brain imaging studies in order to rule out the possibility of cerebral dysgenesis.

There are several causes of gingival hyperplasia and one of the most well-known is drug-induced gingival enlargement. Nevertheless, causes of congenital gingival enlargement include only hereditary and metabolic disorders. Only one case of drug-induced congenital gingival hyperplasia has been reported. We present the second neonate with gingival hyperplasia in the context of foetal valproate syndrome and review the literature.

We present four cases of femoral neuropathy due to urological surgery, first case happened after right lumbotomy twenty years ago and the other three cases in the last four years after iliac incision. We review lesion production mecanism, evolution, treatment and prevention of this rare neurological complication. We do a literature review about this pathology related with urological activity.

Introduction: In 1974 Pena and Shokeir described an early lethal disorder (OMIM 208150) that was characterised by neurogenic arthrogryposis, facial abnormalities and pulmonary hypoplasia. It has recently been suggested that it is secondary to the reduction of movements in the uterus due to an intrinsic pathology regardless of the cause (FADS, foetal akinesia deformation sequence). Klippel-Feil (K-F) syndrome (OMIM 118100) is defined by the congenital fusion of one or two cervical vertebrae, and clinically manifests as a shortened neck, with limited head movements, and may also be associated to other malformations., Case Reports: We report the case of a family diagnosed with K-F syndrome type II. It was observed in the father and one daughter; another child presented Pena-Shokeir type I and died during the neonatal period. Both siblings presented anomalies in the central nervous system., Conclusions: The incidence of FADS syndrome is 1/10,000 deliveries and that of K-F syndrome is between 1/35,000 and 1/42,000 births. We reviewed the literature on FADS syndrome and no familiar association with K-F syndrome was found among its causes. Our aim is to report that an association between the two conditions is possible, which is very important for establishing suitable genetic counselling.

Introduction: Embryogenetic disorders are one of the most serious problems in the life of an epileptic. Over the last few decades many antiepileptic drugs, including valproic acid, have been shown to have teratogenic properties. Embryopathy due to valproate, also known as fetal valproate syndrome, is a well-known and documented example of these conditions., Case Report: We report the case of a preterm newborn infant who, at birth, exhibited a syndrome characterised by facial dysmorphia, gingival hyperplasia, neurological hyperexcitability and multiple malformations, the most striking of which was the presence of predominantly temporal atrophy in the left brain hemisphere. The most significant event in the medical history of the case was the mother's taking valproate in monotherapy throughout the entire period of gestation as treatment for generalised idiopathic epilepsy that was diagnosed during adolescence. Screening precluded the most common metabolic, hereditary or infectious causes that can cause embryopathies., Conclusions: The mother's history of taking valproic acid and the specific findings that coincided in the peculiar embryopathy of this patient enabled us to link them.

Introduction: Polyneuropathies (PNP) result from damage to a number of nerves. They are classified according to the anatomical-functional, histological, aetiological and genetic characteristics. Here we report on the prolonged follow-up carried out on an adult male who had a chronic recurring axonal-type PNP., Case Report: We describe the case of a 65-year-old male who presented episodes of neurological deficit over a period of 10 years that were interspersed with prolonged, stable periods in which he was free of new symptoms. The patient's functional limitations became greater with each successive relapse and the situation is now one of extreme disability. The characteristics of the clinical picture pointed towards a diffuse peripheral nerve disorder, and the neurophysiological studies carried out revealed polyneuropathic, sensory and motor injury mediated by an axonal mechanism with no associated demyelination. A comprehensive analytical, imaging and functional study was conducted, but did not reveal any specific causes. The particular clinical process, the exclusion of other pathologies and the electrophysiological findings allowed us to reach a diagnosis of recurring or episodic chronic primary axonal PNP., Conclusions: This description can be added to the few cases reported in the literature. As we see it, this is an unusual, although probably underdiagnosed, disease and it must be taken into account in the differential diagnosis of chronic recurring PNP because of the diagnostic implications and--with respect to its usually poor response to therapy--due to the prognoses.