Tonic Seizure Status Epilepticus Triggered by Valproate in a Child with Doose Syndrome.

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.

Contribution of a new electrophysiologic test to Morton's neuroma diagnosis.

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.

A 2.84 Mb deletion at 21q22.11 in a patient clinically diagnosed with Marden-Walker syndrome.

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.

Ulnar nerve thickness at the elbow on longitudinal ultrasound view in control subjects.

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.

Posttraumatic neuropathy of the palmar cutaneous branch of the median nerve: four cases. Laceration or entrapment?

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.

Atypical glycine encephalopathy in an extremely low birth weight infant: description of a new mutation and clinical and electroencephalographic analysis.

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.

Intraoperative neurophysiological monitoring of the phrenic nerve: utility and descriptions of the technique. / Monitorización neurofisiológica intraoperatoria del nervio frénico: utilidad y descripción de la técnica.

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.

Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).

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.

[Polyneuropathies in the elderly. Classification and thematic review]. / Polineuropatías en la población anciana. Clasificación y revisión temática.

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.

Exceptional response to brivaracetam in a patient with refractory idiopathic generalized epilepsy and absence seizures.

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.

Uniparental disomy as a cause of spinal muscular atrophy and progressive myoclonic epilepsy: phenotypic homogeneity due to the homozygous c.125C>T mutation in ASAH1.

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.

EEG characterization of audiogenic seizures in the hamster strain GASH:Sal.

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.

[Value of simultaneous electromyographic recording of the levator palpebrae and the orbicularis oculi muscles as an early diagnostic marker for blepharospasm]. / Aportación del registro electromiográfico simultáneo del levator palpebrae y el orbicularis oculi como marcador diagnóstico precoz de blefaroespasmo.

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.

Periodic Lateralized Epileptiform Discharges (PLEDs) and pneumococcal meningoencephalitis.

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.

[Multiple mononeuritis and eosinophilic fasciitis in a patient with idiopathic hypereosinophilic syndrome]. / Mononeuritis múltiple y fascitis eosinofílica en una paciente con síndrome hipereosinofílico idiopático.

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.

Opposite caudal versus rostral brain nitric oxide synthase response to generalized seizures in a novel rodent model of reflex epilepsy.

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.