Sensitivity of candling as routine method for the detection and recovery of ascaridoids in commercial fish fillets.

Ascaridoids are one of the main parasitic hazards in commercial fish. Candling is the current industrial screening method whereby visible ascaridoid larvae are detected on a light table and manually removed. The aim of this study was to assess the sensitivity (Se) and negative predictive value (NPV) of this method. To make targeted recommendations to the fish industry, the Se was calculated per fish part, larval genus, and fish species. All fish parts (n = 615) were first candled, and larvae were collected, followed by enzymatic digestion to recover the remaining larvae. A fish part was considered positive if at least one larva was detected using candling and/or enzymatic digestion, with both methods combined as reference standard. The overall Se of candling was 31% (95% CI 23-41%) and NPV was 87% (95% CI 85-90%). The Se increased with higher numbers of larvae/100 g infected muscle. A low NPV was found for the belly flaps, therefore we either advise the removal or proper freezing of this part. Lastly, the Se and larval recovery was the highest for the darker and larger Pseudoterranova spp. larvae. Due to the low overall efficacy of candling, further assessment of its cost-benefit and impact on consumers' health risk should be conducted.

High occurrence of Anisakidae at retail level in cod (Gadus morhua) belly flaps and the impact of extensive candling.

The presence of Anisakidae at retail level, after the routine screening via candling, was investigated in cod, the most commonly consumed fish species in Belgium. A total of 780 pre-packed belly flap samples destined for one branch of retail shops were collected from a Belgian wholesale company. To recover all larvae, each sample was first candled and thereafter enzymatically digested. Larvae were morphologically identified to the genus level and a subset was additionally molecularly confirmed by amplification of the ITS fragment and HinfI/HhaI enzyme restriction. The PCR/RFLP profiles of Contracaecum spp. were determined and confirmed with sequencing by the European Reference Laboratory for Parasites (Istituto Superiore di Sanità). The positivity rate of Anisakidae in the individual cod samples was 18% [95%-CI: 15-21%], with a mean intensity of one larva [range: 1-6]. Belly flaps were sold packed primarily by two, with a one-in-three chance of buying an infected package. Pseudoterranova spp. infections (single infections) were most frequently detected (positivity rate 9% [95%-CI: 7-11]), closely followed by Anisakis spp. (7% [95%-CI: 6-9]). Co-infections of Pseudoterranova spp. and Anisakis spp. comprised 8% of the infections, with a positivity rate of 1% [95%-CI: 1-3%]. All belly flaps reportedly were candled prior to our sampling, nonetheless our results indicated that an additional candling screening before packaging would identify an extra third of the infections and larvae. In 19 of the 139 infected samples, all larvae were recovered by the additional candling, thereby removing the infection risk for consumers. In conclusion, this study shows that cod belly flaps infected with zoonotic parasites reach the Belgian consumer. Although a second candling step at retail level could be helpful in reducing the consumer risk, additional measures are needed since 66% of infections would still remain undetected.

Ascaridoids in commercial fish: Occurrence, intensity and localization in whole fish and fillets destined for the Belgian market.

Anisakidae and Raphidascaridae are marine nematodes present in a wide range of fish hosts, which may cause gastro-intestinal complaints and/or allergy in human, in addition to economic losses for the industry. Data regarding the presence of these parasites in fish for the Belgian market is currently missing; therefore, our aim was to investigate the presence and intensity of ascaridoids in a wide range of commercially fish species. A total of 415 fish samples, belonging to 36 different fish species, were collected from a Belgian whole-sale company. Ascaridoid larvae from the viscera (if present) and the muscles were collected by enzymatic digestion and the prevalence, median intensity, mean number of larvae per 100 g infected muscle, and localisation were determined. An overall prevalence of 53% [95%-CI: 42-63%] in the viscera and 27% [95%-CI: 23-32%] in the muscles was observed. Infection in the muscles varied between the fish species; no larvae were detected in 13 fish species, while a high prevalence (>78%) was observed in pollack, halibut, and gurnard. Most samples originated from the Northeast Atlantic Ocean, with the highest prevalence in the muscles observed in the Barents & Norwegian Sea (65% [95%-CI: 38-86]). Muscle samples were, if possible, divided in an anterior region, belly flap, medial region, and posterior region, with the most infections and larvae found in the belly flaps. In all samples, a total of 2569 larvae were recovered, with 1594 larvae originating from the viscera and 975 from the muscles; with an average of two larvae per 100 g infected fillet detected. Larvae were morphologically identified, and a subgroup was further confirmed using PCR/RFLP, resulting ultimately in the identification of Anisakis simplex s.s. (1853 larvae), A. pegreffii (137), A. simplex/pegreffii hybrid genotype (38), Pseudoterranova decipiens (160) and Hysterothylacium aduncum (380). This study demonstrates that ascaridoid larvae are highly prevalent in different fish species on the Belgian market.

Prebiotics and phytogenics functional additives in low fish meal and fish oil based diets for European sea bass (Dicentrarchus labrax): Effects on stress and immune responses.

The use of terrestrial raw materials to replace fish meal (FM) and fish oil (FO) in marine fish diets may affect fish growth performance and health. In the last years functional additives have been profiled as good candidates to reduce the effects on health and disease resistance derived from this replacement, via reinforcement of the fish immune system. In the present study, three isoenergetic and isonitrogenous diets with low FM and FO (10% and 6% respectively) were tested based on supplementation either with 0.5% galactomannanoligosaccharides (GMOS diet) or 0.02% of a mixture of essential oils (PHYTO diet), a non-supplemented diet was defined as a control diet. Fish were fed the experimental diets in triplicate for 9 weeks and then they were subjected to a stress by confinement as a single challenge (C treatment) or combined with an experimental intestinal infection with Vibrio anguillarum (CI treatment). Along the challenge test, selected stress and immunological parameters were evaluated at 2, 24 and 168h after C or CI challenges. As stress indicators, circulating plasma cortisol and glucose concentrations were analyzed as well as the relative gene expression of cyp11b hydroxylase, hypoxia inducible factor, steroidogenic acute regulatory protein, heat shock protein 70 and heat shock protein 90 (cyp11b, hif-1α, StAR, hsp70 and hsp90). As immune markers, serum and skin mucus lysozyme, bactericidal and peroxidase activities were measured, as well as gene expression of Caspase-3 (casp-3) and interleukin 1ß (il-1ß). The use of functional additives induced a significant (p < 0.05) reduction of circulating plasma cortisol concentration when confinement was the unique challenge test applied. Supplementation of PHYTO induced a down-regulation of cyp11b, hif-1α, casp-3 and il-1ß gene expression 2h after stress test, whereas StAR expression was significantly (p < 0.05) up-regulated. However, when combination of confinement stress and infection was applied (CI treatment), the use of PHYTO significantly (p < 0.05) down-regulated StAR and casp-3 gene expression 2h after challenge test, denoting that PHYTO diet reinforced fish capacity of stress response via protection of head kidney leucocytes from stress-related apoptotic processes, with lower caspase-3 gene expression and a higher il-1ß gene expression when an infection occurs. Additionally, dietary supplementation with GMOS and PHYTO compounds increased fish serum lysozyme after infection. Both functional additives entailed a better capability of the animals to cope with infection in European sea bass when fed low FM and FO diets.

Presence of Anisakidae in commercial fish species imported into the Belgian food markets: A systematic review and meta-analyses.

Anisakidae are marine zoonotic nematodes with most commercial fish species as intermediate hosts. Both public health risks and socio-economic problems are attributed to these larvae. Despite these concerns, the occurrence of Anisakidae in commercial fish species in Belgium remains unknown. Therefore, the main objective of this systematic review was to look into studies assessing the prevalence and intensity (level of infection) of Anisakidae in countries importing fish to the Belgian market. The databases of PubMed, Web of Science, Cordis, Google Scholar, Google, African Journals online and Asia Journals online were searched. Main eligibility criteria were: fish species consumed in Belgium; studies conducted in one of the main importing countries; and the availability of prevalence data. From the original 519 identified studies, 83 were included with data from Spain, Germany, Chile, Denmark, Turkey, France, China, England, Belgium, Norway, Iceland, Senegal and Sweden. Overall results show a widespread occurrence of Anisakidae with a high variability in prevalence between fish species and fishing sea. Cod (Gadus morhua) and Atlantic salmon (Salmo salar), the most consumed fish species in Belgium, have a mean prevalence of 33% and 5% respectively. Of all investigated fishing zones, fish caught in the Northeast Atlantic has the highest rate of infection (68%). Furthermore, higher prevalences were found when looking at the viscera (mean prevalence 59%) compared to the muscle (29%) and with superior techniques such as enzymatic digestion or UV press (46%) compared to candling, the routine method (23%). Farmed fish were found to be the least infected (2%) but were still not Anisakidae free. The widespread presence of Anisakidae and the associated food safety implications indicate the need to further investigate the presence of Anisakidae in fish in the Belgian market.

The cuff method: a pilot study of a new method of monitoring neuromuscular function.

BACKGROUND: A new method of monitoring neuromuscular blockade based on a modified blood pressure cuff that incorporates stimulating electrodes was compared with mechanomyography (MMG) ('gold standard'). METHODS: Forty adults and 20 children (ASA I-II) underwent neuromuscular blockade monitoring on the contralateral arms and on the same arm using the new cuff method and MMG. Only train-of-four (TOF) ratios > 0.1 and T(1) heights > 0 were studied. Supramaximal stimulation was also assessed. A device based on a PC with an analogue-to-digital conversion card was used to control and synchronize MMG and the cuff method. The agreement between both methods was assessed using the statistical method of Bland and Altman. RESULTS: When TOF ratios were >0.7, the bias between the two methods was -0.04 with the limits of agreement ranging from -0.21 to -0.12 (95% CI -0.06 to -0.02). The T(1) > 0 heights bias was -0.01 with the limits of agreement ranging from -0.26 to 0.24 (95% CI -0.02 to -0.003). The sensitivity of the cuff method was 88%, with a specificity of 85% and an accuracy of 86%. CONCLUSION: This pilot study indicates that the cuff method could be useful to monitor neuromuscular blockade according to the bias and limits of agreement compared with MMG, particularly when the degree of blockade was evaluated by TOF ratios > 0.7. The new cuff method is easy and simple to use. However, further studies in a larger number of patients are necessary to confirm these favourable preliminary results.

[Oculopharyngeal muscular dystrophy: study of patients from seven Spanish families with different GCG expansions in PABP2 gene]. / Distrofia muscular oculofaríngea: estudio de pacientes pertenecientes a siete familias españolas con diferentes expansiones GCG en el gen PABP2.

INTRODUCTION: Autosomal dominant oculopharyngeal muscular dystrophy (OPMD), with late onset due to ptosis and/or dysphagia, is caused by short (GCG)8-13 triplet-repeat expansions in the polyadenylation binding protein 2 (PABP2) gene, which is localized in chromosome 14q11. The severity of the dominant OPMD as well as the number of expansions that cause the disease are variable. (GCG)9 is mentioned as the most frequent and the genotype/phenotype has still not been well-determined. OBJECTIVE: To describe the type of expansions (GCG)n found in Spanish families with OPMD, establishing if there is variability of them and the possible geno-phenotypical correlations. METHODS: Clinicopathological and molecular studies have been performed in 15 consecutive patients, belonging to seven Spanish families with OPMD. The muscular biopsy study under electronmicroscopy shows intranuclear inclusions (INIs) in all the examined patients (one patient per family). The genetic findings confirm the cause of the disease in all the affected members and in one clinically asymptomatic member of one recently examined family: three families (six, one and one studied members, respectively) present the (GCG)9 expansion, two families (one studied member each one) present the (GCG)10 expansion and two families (one and four studied members respectively) present the (GCG)11 expansion. In these 15 patients with a short GCG expansion causing OPMD, clinical tests for OPMD and a follow-up study of their clinical course have been carefully assessed: in patients with the (GCG)9 expansion major abnormalities appeared in extrinsic ocular mobility and more precocious presentation of limb girld (lumbopelvic preferentially) weakness leading to a great disability before the seventh decade of life under the seventies in some patients and sometimes leading to death. In patients with (GCG)10 and (GCG)11 expansions, eye movements are always preserved and the limb girld muscles weakness did not appear before the seventh decade. No correlation seems to exist between age of onset of the ptosis or dysphagia and the different (GCG)n expansions and the surgical treatment of ptosis, performed in eight patients, showed good results independently of the (GCG)n mutation. CONCLUSIONS: Although further clinical and genetic studies are necessary to establish a strict genotype/phenotype correlation in OPMD, we concluded that the (GCG)9 expansion involve more severe phenotypes than those related to the (GCG)10 or (GCG)11 expansions. Therefore, genetic testing could benefit prognosis in asymptomatic individuals.

SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I.

Hereditary sensory neuropathy type I (HSN I) is an autosomal dominant ulceromutilating disorder of the peripheral nervous system characterized by progressive sensory loss. HSN I locus maps to chromosome 9q22.1-22.3 and is caused by mutations in the gene coding for serine palmitoyltransferase long-chain base subunit 1 (SPTLC1). A novel missense mutation in exon 13 of the SPTLC1 gene (c.1160G-->C; p.G387A) in twin sisters with a severe HSN I phenotype is reported.

Comparison of three different volumes of mepivacaine in axillary plexus block using multiple nerve stimulation.

BACKGROUND: The multiple injection technique for axillary block, in which the four distal nerves of the plexus are located by a nerve stimulator and separately injected, has been shown to provide a high success rate and a short onset time. This randomized double-blind study was conducted to compare the effectiveness of three different volumes of mepivacaine 10 mg x ml(-1) in patients undergoing elective distal upper limb surgery under axillary brachial plexus block with the four-nerve approach. The number of complete sensory blocks was the primary efficacy variable. METHODS: A total of 114 adult patients were randomly allocated to receive 36 (n=38), 28 (n=38), and 20 ml (n=38) of mepivacaine 10 mg x ml(-1). In each group, volumes were equally distributed in the four nerve territories. In all patients, performance time, latency time, block characteristics, need of supplementary blocks, tourniquet tolerance, duration of analgesia, and complications were recorded. RESULTS: Complete sensory block was obtained in 97% of patients receiving a volume of 36 ml, 97% of those receiving 28 ml, and 94% of those receiving 20 ml. One patient in the group of 28 ml and five patients in the group of 20 ml experienced pain on inflation of the tourniquet. Two months after surgery, no case of postoperative neurological dysfunction was observed. CONCLUSIONS: The three volumes (38, 28, and 20 ml) of mepivacaine 10 mg x ml(-1) ensured a similar and high percentage of complete sensory blocks in axillary brachial plexus anaesthesia with nerve stimulation involving the location of four motor responses.

[Crazy laughter: first manifestation of a pontine tumour]. / "Risa loca": primera manifestación de un tumor protuberancial.

Crazy laughter (<>) was first described in 1903 as a prodromic symptom of an ischemic stroke and was later associated with brain lesions having a different location and etiology. We describe the case of a patient with a poorly differenciated pulmonary carcinoma who presented a centropontine image consistent with metastasis, whose initial manifestation was involuntary, persistent and unmotivated laughter that preceded other clinical manifestations. We revised, on the one hand, previous cases described in the literature of pathological laughter in relationship to structural lesions, of vascular or neoplastic etiology, and, on the other, the nervous centers and pathways that control the laughter mechanism.

[Hereditary neuropathy with liability to pressure palsies: study of six Spanish families]. / Neuropathies héréditaires sensibles à la pression: étude de six familles espagnoles.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited demyelinating neuropathy typically characterized by recurrent episodes of acute painless peripheral nerve palsies often preceded by minor trauma or compression at entrapment sites. However, less classical phenotypes have been reported. A 1.5 Mb deletion in chromosome 17 p11.2 has been shown to be the genetic basis of the disease in the majority of HNPP patients. The few families without this deletion harbored a mutation in the PMP22 gene. We performed a clinical, neurophysiological and molecular genetic study of 6 Spanish HNPP families. Five families (22 individuals) showed the classical chromosome 17 p11.2 deletion and one family (3 individuals) had a novel 3'splice-site mutation in PMP22. Neurophysiological abnormalities were detected in all symptomatic (n=21) and asymptomatic (n=4) deletion or mutation carriers, even in childhood. In addition to the typical presentation we observed other phenotypes: recurrent focal short-term sensory symptoms, a progressive mononeuropathy, a Charcot-Marie-Tooth (CMT) disease-like chronic progressive polyneuropathy, a chronic sensory polyneuropathy and a chronic inflammatory demyelinating polyneuropathy. We report new or very rare phenotypesThese atypical clinical aspects and intrafamilial heterogeneity are present in families with the HNPP deletion as well as in the family with the PMP22 mutation. However, the CMT disease-like chronic polyneuropathy was more common in the PMP22 mutation family. Intrafamilial heterogeneity also seemed to be more pronounced in this kinship. Patients in this family had a mild chronic motor and sensory polyneuropathy neurophysiologically characterized by delayed distal latencies, reduced nerve conduction velocities (NCV) within the demyelinating range, mildly decreased amplitudes of motor and sensory evoked potentials and absence of conduction blocks. In contrast, patients with the common HNPP deletion, regardless of their phenotype, had a diffuse increase in distal motor latencies contrasting with moderately reduced motor NCVs, preserved sensory nerve action potentials, slowing of NCVs at the common entrapment sites and occasionally conduction blocks. In this study we confirm the clinical and molecular heterogeneity of HNPP, emphasizing the need for a mutation analysis of the PMP22 gene when the common 17p11.2 deletion is not found in clinically suspected HNPP patients. We conclude that the 3'splice-site mutation in PMP22 and the common HNPP deletion have largely the same functional consequences although some clinical and neurophysiological differences were observed.

[Familial myopathy with desmin storage seen as a granulo-filamentar, electron-dense material without mutation of the alphabeta-crystallin gene]. / Miopatía familiar con sobrecarga de desmina, bajo forma de material granulofilamentoso denso en microscopia electrónica, sin mutación en el gen de la alphabeta-cristalina.

BACKGROUND: Desmin-related myopathy is a familial myopathy and cardiomyopathy. Three subgroups have been outlined, an autosomal dominant (AD) granulofilamentous type with cardiomyopathy, an AD cytoplasmic/spheroid inclusion body type and an autosomic recessive Mallory body-like inclusion type. Recently, in one family belonging to the first group it has been identified a mutation within a gene coding for a chaperone protein, alphabeta-crystallin (CRYAB gene). OBJECTIVE: To describe a Spanish family with a desmin-related myopathy, an AD granulofilamentous type with cardiomyopathy, with a molecular study that does not express any point mutation in the CRYAB gene. PATIENTS, METHODS AND RESULTS: This report concerns a family from southern Spain in which 2 sisters (37 and 44 and 36 years old respectively) present an involvement of skeletal (distal more than proximal) and velo-pharyngeal muscles with onset at the third decade of life and with a rather severe progression, leading soon to bilateral foot drops. The mode of transmission is autosomal dominant. Two other members, the mother and one brother _the latter with hypertrophic cardiomyopathy, atrioventricular block and severe heart failure_, have already died. The electrophysiological study carried out in the sisters shows myogenic patterns with abundant spontaneous activity but not genuine myotonic discharges. Muscle biopsy, also purchased in both sisters, shows myopathic changes, a few rimmed vacuoles in one of them, and several "rubbed-out" fibers or fibers "effacées" visible within the intramyofibrilary network on the enzymatic stainings. The ultrastructural findings in both biopsies reveal a similar pattern of structural damage: an intrasarcoplasmic (specially subsarcolemmal) accumulation of an electro-dense filamentous material arising from the Z-bands and a focal disruption of the myofibrils. Immunohistochemically the subsarcolemmal material stained positively for the intermediate filament protein desmin but other proteins as ubiquitin, tropomyosine and actin were found overexpressed. Genetic studies have excluded myotonic dystrophy, any point mutation in the CRYAB gene, and different markers failled to express linkage to any loci on chromosome 12. The possible mutations in desmin gene are to be studied. CONCLUSION: The distinct intrafamilial phenotype observed in this family confirms the multisystemic character of the desmin-related myopathyies. The genetic results also support the genetic heterogeneity of these myopathies and reinforce the concept that mutations in the desmin gene must be investigated as a cause of the disease.

A novel 3'-splice site mutation in peripheral myelin protein 22 causing hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant, demyelinating peripheral neuropathy. Clinical hallmarks are recurrent painless focal neuropathies mostly preceded by minor trauma or compression at entrapment sites of peripheral nerves. In the majority of the patients, HNPP is caused by a 1.5 Mb deletion on chromosome 17p11.2-p12 containing the peripheral myelin protein 22 (PMP22) gene. Point mutations within this gene are reported in only a few families. We report a novel mutation in the PMP22 gene in a Spanish family with HNPP. The mutation is a 3' splice-site mutation, preceding coding exon 3 (c.179-1 G>C), causing a mild HNPP phenotype.

[Acquired dysimmune neuropathies. Clinical symptoms and classification]. / Neuropatías disinmunes adquiridas. Sintomatología clínica y clasificación.

INTRODUCTION: The neuropathies caused by dysimmunity have seen great changes in recent years. The different forms of clinical presentation, electrophysiological expression, associated anomalies seen on analytical tests, particularly the presence of antibodies to the various antigens of myelin are becoming better understood. This confirms their dysimmune nature and also offers unforeseen possibilities for the comprehension of etiopathogenic mechanisms and possible classifications of specific etiopathogenic factors. DEVELOPMENT: Based mainly on our own experience, in this paper we review current concepts of the three main dysimmune polyneuropathies, the Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuritis or CIDP and the motor multifocal neuropathies (MMN) with block-conduction or Lewis-Summer syndrome. Regarding the first condition, we particularly emphasize the convenience of establishing the broad classification needed by the variation in its clinical presentation, with regional and functional variants: among the latter we consider particularly the pure motor forms which in most cases are axonal forms with an etiopathogenic basis which is fairly well established and almost constantly associated with the presence of specific antibodies in the serum of patients with this condition. With reference to CIDP, we discuss the existence of atypical forms and the frequency of the relapsing form concerning the evolution. The MMN are the most recently discovered dysimmune neuropathies, according to both the literature and personal experience. We try to establish the difference between pure motor forms and those which also have sensory involvement (or MADSAM) and are called the Lewis-Sumner syndrome.

[Acute posterior cord lesions in multiple sclerosis. An MRI study of the clinical course in 20 cases]. / Lésions cordonales postérieures aiguës dans la sclérose en plaques.Etude clinico-évolutive et par IRM de 20 cas.

Twenty patients with multiple sclerosis (MS), 19 women and 1 man, with acute proprioceptive sensory disturbances related to the presence of plaques on the posterior columns (posterior column syndrome) at the cervical or thoracic levels of the spinal cord, were selected among 138 new patients with MS assisted in our neurological unit over the past five years. In 17 of these patients, the acute posterior cordonal syndrome was responsible for the first clinical manifestations of the disease. The other 3 patients had a history suggestive of MS. These 20 patients were followed with a minute analysis of neurological function with repeated clinical evaluation combined with repeated MRI study of the spinal cord. Brain MRI (strongly suggestive of MS in 15 patients), evoked potentials (EP) and cerebrospinal fluid electrophoresis analysis (with oligoclonal bands present in all patients were it was performed) were also obtained at least once in each patient. Spinal cord MRI demonstrated more lesions in the cervical region (90 p.100) than in the thoracic regions (10 p.100). Eighty percent of the cervical lesions were located high, between C1 and C4. The most characteristic clinical expression was the deafferentation of one upper limb, preferentially the "useless hand" (Oppenheim) or even a pseudoathetosic or dystonic limb. Propioceptive ataxia or spontaneous cervical or brachial pain were other forms of clinical expression. No major motor deficit or sphincter disorders were noted at any time in the clinical course in any of the patients. There was a good correlation between localization and morphology of the plaques detected by spinal cord MRI and clinical signs. Intrinsic medullary lesions were seen as high intensity signals on T2-weighted images which were enlarged more than the same lesion visualized on T1-weighted images after injection of paramagnetic contrast agents. This reflected the presence of edema extending beyond the main inflammatory lesion. There was also a good correlation between improvement of clinical symptoms and total or, mor frequently, partial reduction of the plaques, analyzed morphologically by successive spinal cord MRI series. The diagnosis of MS was clinically definitive in 60 p.100 of cases and laboratory-supported definitive in 40 p.100. During the follow-up period (average 36 months), 15 patients (75 p.100) presented one or more exacerbations, all of them presenting a favorable course: at last follow-up, 9 patients were asymptomatic, EDSS was 1 in 6 patients, 1.5 in 4 patients and 2 in 1 patient. This study confirms the contribution of serial spinal cord MR studies to understanding the natural history and pathophysiology of medullary forms of MS presenting as a cordonal posterior syndrome. It also shows a good relationship between the clinical manifestations and course of this form of MS and the localization and variable morphology of plaques. Finally, our results suggest the predictive benign course for this medullary form of MS that seems to be almost exclusively restricted to the female gender.

Genetic refinement of the hereditary neuralgic amyotrophy (HNA) locus at chromosome 17q25.

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal neuropathy. HNA is characterised by episodes of painful brachial plexus neuropathy with muscle weakness and atrophy, as well as sensory disturbances. Single episodes are commonly preceded by non-specific infections, immunisations or parturition. Mild dysmorphic features and short stature are present in some HNA families, but absolute co-segregation with HNA has not been described. To refine the previously described HNA locus on chromosome 17q25, we performed a genetic linkage study in five HNA families with different geographic origins. Significant linkage was obtained with chromosome 17q24-q25 short tandem repeat (STR) markers in three HNA families and suggestive linkage was found in the other two HNA families. Analysis of the informative recombinations in affected individuals allowed us to reduce the HNA linkage interval to a candidate region of 3.5 cM.

Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic).

Congenital myasthenic syndrome (CMS) with end-plate acetylcholinesterase (AChE) deficiency is a rare autosomal recessive disease, recently classified as CMS type Ic (CMS-Ic). It is characterized by onset in childhood, generalized weakness increased by exertion, refractoriness to anticholinesterase drugs, and morphological abnormalities of the neuromuscular junctions (NMJs). The collagen-tailed form of AChE, which is normally concentrated at NMJs, is composed of catalytic tetramers associated with a specific collagen, COLQ. In CMS-Ic patients, these collagen-tailed forms are often absent. We studied a large family comprising 11 siblings, 6 of whom are affected by a mild form of CMS-Ic. The muscles of the patients contained collagen-tailed AChE. We first excluded the ACHE gene (7q22) as potential culprit, by linkage analysis; then we mapped COLQ to chromosome 3p24.2. By analyzing 3p24.2 markers located close to the gene, we found that the six affected patients were homozygous for an interval of 14 cM between D3S1597 and D3S2338. We determined the COLQ coding sequence and found that the patients present a homozygous missense mutation, Y431S, in the conserved C-terminal domain of COLQ. This mutation is thought to disturb the attachment of collagen-tailed AChE to the NMJ, thus constituting the first genetic defect causing CMS-Ic.

[Transmyocardial revascularization with laser]. / Revascularización transmiocárdica con láser.

Patients with severe angina pectoris, refractory to medical treatment, in which conventional revascularization (PTCA or bypass surgery) is not possible because they present advanced coronary artery disease with a poor distal bed, account for an important clinical problem due to an increasing incidence, combined with poor quality of life, an elevated risk of severe complications, repeated hospital admissions and high mortality rate. Laser transmyocardial revascularization provides a new therapeutic alternative for these patients. Although up to now there are only a few published series, with a small number of patients, the results obtained in the two ongoing multicentric studies in Europe and the United States (including more than 500 patients at present) are quite promising. It is a simple surgical procedure, but its associated mortality is not to be dismissed (in the beginning 12% and currently 5%), because patients are in an advanced evolutionary stage. In Spain this procedure has been available since April 1996 and the results have been encouraging. In our small series we have noted a significant symptomatic improvement and better quality of life.