Functional and surgical treatments in patients with spinal muscular atrophy (SMA).

Spinal muscular atrophies (SMA type 1, 2, 3) present with various severities according to the motor semeiology related to lesions of the peripheral nervous system (lesions of the anterior horn cells motoneuron or even brain stem). Early motor deficiency causes skeletal deformities responsible for the alteration or even absence of motor skills acquisition. The management of these patients involves several practitioners: pediatric neurologist, pediatric pneumologist, physical medicine and rehabilitation therapist, pediatric orthopedic surgeon, psychologist, physiotherapist, etc. Therefore, this multidisciplinary management must take place in a reference center. This has allowed for improvement of the natural history of SMA. Despite the severity of clinical presentation, especially in SMA type 1 or 2, the functional aspect is always to be taken into account in the first instance. Furthermore, the natural history of the disease is currently being modified by the emergence of innovative therapies that will change the evolution of the disease and its management. Indeed, current treatment objectives are the comfort of installation and the fight against neuro-orthopedic degradation. Although the rise in the number of innovative therapies has led to increased expectancies, such as motor function improvement, practitioners should be aware that these innovative treatments should be balanced against child development and the disease's natural history. Scoliosis surgery is almost systematic in SMA type 2 because of trunk muscular deficiency, especially intercostal muscle insufficiency, and spino-pelvic complex disorder. However, surgical techniques have evolved to become less invasive and more growth friendly in order to follow child development. The final goal of surgery in SMA patients is to obtain a 3-dimensional deformity correction along with a spino-pelvic realignment in order to allow for a comfortable seated position, which is the position of function in these patients, and to allow for better ventilation. Faced with this global approach and innovative therapies, global assessment is warranted not solely in an isolated manner, as is usually the case during hospital stays with traditional scales, but rather during daily activities. This is the case of daily monitoring, which allows for motor skill and activity assessments throughout the day. The principle is to characterize, according to SMA type and treatment, the activity type (standing, seated, walking), duration, intensity and frequency. The ultimate goal would be to identify the variety and occurrence of motor activities, and finally to clarify if the different treatments, including innovative therapies, lead to functional improvement in these patients. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Management of drooling in children with cerebral palsy: A French survey.

AIM: To characterise children with cerebral palsy (CP) and pathological drooling in France, and to describe care pathways, assessment and treatment. METHOD: A transversal, observational, descriptive survey of the practices and opinions of 400 health professionals potentially involved in the care of children with CP, was carried out nationally across France in 2013. RESULTS: The response rate was 36%. Seventy-five questionnaires were returned and analysed (52%). A small proportion of children were specifically treated for drooling (<25%). Assessments were carried out in 75% of cases and 91% of professionals prescribed treatments. Use of assessment tools varied widely. The most common treatment was oro-facial rehabilitation (95% of professionals), followed by anticholinergic drugs (Scopolamine(®)) (94%) botulinum toxin injections (BT) (66%) and surgery (34%). Scopolamine was considered to be less effective than BT and to have more side effects. CONCLUSION: The rate of pathological drooling in children with CP is likely underestimated and under treated in France. There is a lack of knowledge regarding assessment tools. Aside from rehabilitation, current practice is to prescribe medication as the first-line treatment, however professionals consider that BT is more effective and has less side effects.

Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists.

To investigate the relationship between survival in colorectal cancer patients and the number of lymph nodes examined by a pathologist, previously attributed to stage migration, we used data from a cohort of 5174 colorectal cancer patients recruited between September 1991 and August 1994, and followed-up for 5 years. We selected cases with data present on all prognostic variables, and stratified them into three groups by number of nodes examined. We made a multivariate survival comparison using a Cox regression model. In all, there were 3592 cases with data present on all prognostic variables. Patients who had >10 nodes identified had a significant survival advantage over those who had 5-10 identified, who had in turn a similar advantage over those with 0-4 identified (P<0.001). This effect was present in the whole group and at all Dukes' stages, although statistically significant only in stages B (P=0.004) and C (P=0.019). The effect remained after adjustment in a Cox regression model in which the mean number of nodes taken out by each surgical firm did not predict survival. In a sub-group with data on lymphocytic infiltration into the primary tumour a survival advantage was noted in those with prominent rather than mild infiltration (P<0.001): the former also tended to have more nodes found (P=0.015). Stage migration alone cannot explain these results, as survival advantages are noted across the whole population independent of stage. Lymphocytic infiltration into the primary tumour is prognostically important, and is associated with the number of nodes found. Reactive enlargement of lymph nodes in the mesentery may make them easier to find, reflect immune response to the tumour, and thus indirectly impact upon survival.

Sagittal alignment of spine and pelvis regulated by pelvic incidence: standard values and prediction of lordosis.

Pelvis and spinal curves were studied with an angular parameter typical of pelvis morphology: pelvic incidence. A significant chain of correlations between positional pelvic and spinal parameters and incidence is known. This study investigated standards of incidence and a predictive equation of lordosis from selective pelvic and spinal individual parameters. One hundred and forty nine (78 men and 71 women) healthy adults, aged 19-50 years, with no spinal disorders, were included and had a full-spine lateral X-ray in a standardised upright position. Computerised technology was used for the measurement of angular parameters. Mean-deviation section of each parameter and Pearson correlation test were calculated. A multivariate selection algorithm was running with the lordosis (predicted variable) and the other spinal and pelvic parameters (predictor variables), to determine the best sets of predictors to include in the model. A low incidence (<44 degrees ) decreased sacral-slope and the lordosis is flattened. A high incidence (>62 degrees ) increased sacral-slope and the lordosis is more pronounced. Lordosis predictive equation is based on incidence, kyphosis, sacral-slope and +/-T9 tilt. The confidence limits and the residuals (the difference between measured and predicted lordosis) assessed the predicted lordosis accuracy of the model: respectively, +/-1.65 and 2.41 degrees with the 4-item model; +/-1.73 and 3.62 degrees with the 3-item model. The ability of the functional spine-pelvis unit to search for a sagittal balance depended both on the incidence and on the variation section of the other positional parameters. Incidence gave an adaptation potential at two levels of positional compensation: overlying state (kyphosis, T9 tilt), underlying state (sacral slope, pelvic tilt). The biomechanical and clinical conditions of the standing posture (as in scoliosis, low back pain, spondylisthesis, spine surgery, obesity and postural impairments) can be studied by comparing the measured lordosis with the predicted lordosis.

Sensori-motor adaptation to knee osteoarthritis during stepping-down before and after total knee replacement.

BACKGROUND: Stepping-down is preceded by a shift of the center of mass towards the supporting side and forward. The ability to control both balance and lower limb movement was investigated in knee osteoarthritis patients before and after surgery. It was hypothesized that pain rather than knee joint mobility affects the coordination between balance and movement control. METHODS: The experiment was performed with 25 adult individuals. Eleven were osteoarthritic patients with damage restricted to one lower limb (8 right leg and 3 left leg). Subjects were recruited within two weeks before total knee replacement by the same orthopedic surgeon using the same prosthesis and technics of surgery. Osteoarthritic patients were tested before total knee replacement (pre-surgery session) and then, 9 of the 11 patients were tested one year after the surgery when re-educative training was completed (post-surgery session). 14 adult individuals (men: n = 7 and women: n = 7) were tested as the control group. RESULTS: The way in which the center of mass shift forward and toward the supporting side is initiated (timing and amplitude) did not vary within patients before and after surgery. In addition knee joint range of motion of the leading leg remained close to normal before and after surgery. However, the relative timing between both postural and movement phases was modified for the osteoarthritis supporting leg (unusual strategy for stepping-down) before surgery. The "coordinated" control of balance and movement turned to be a "sequential" mode of control; once the body weight transfer has been completed, the movement onset is triggered. This strategy could be aimed at shortening the duration-time supporting on the painful limb. However no such compensatory response was observed. CONCLUSION: The change in the strategy used when supporting on the arthritis and painful limb could result from the action of nociceptors that lead to increased proprioceptor thresholds, thus gating the proprioceptive inputs that may be the critical afferents in controlling the timing of the coordination between balance and movement initiation control.

[Progression of cerebral venous thromboses. A retrospective study]. / Evolution des thromboses veineuses cérébrales. Une étude rétrospective.

OBJECTIVES: The management of patients with presumed cerebral venous thrombosis has been recently modified by magnetic resonance imaging and evidence that the early use of heparin decreases mortality and morbidity. Long term outcome of patients with cerebral venous thrombosis (CVT) has rarely been described. We present the results of a follow-up study. METHODS: Twenty patients admitted between 1987 and 1999 for CVT were retrospectively studied. Outcome and follow-up were obtained from direct observation or telephone interviews. RESULTS: There were 16 women and 4 men aged a mean of 39 years (range: 19 to 72). The population was followed-up for a mean of 34 months (range: 12-96). All the patients were initially treated with full-dose heparin. Thirteen of the 20 patients (65%) exhibited no after effects. Seven patients (35%) remained neurologically impaired. The outcome of clinical forms with intracranial hypertension appeared better, but the existence of an initial neurological deficit is of poor prognosis. The small cohort in our series did not permit us to identify other poor prognostic factors. One patient (5%) exhibited subsequent epilepsy. Only one patient (5%) suffered for a second CVT. One patient died from an ovarian neoplasm. No systemic venous thromboembolic relapse was reported. Three patients had non complicated pregnancies. CONCLUSION: Recurrent CVT and systemic venous thrombo-embolic episodes are rare although heparin treatment was suspended early in more than half of the patients. This would question the indication of long-term antivitamin K, which is clearly indicated in auto-immune diseases but is debatable in cases of thrombophilia.

[Belated diagnosis of medullar compression in a case of post-polio syndrome]. / Découverte tardive dune compression médullaire à loccasion de la prise en charge dun syndrome post-polio.

The physiatrist observes about his practice individuals with sequela of old poliomyelitics. A part of them have unusual fatigue and muscular pains and weakness. The hypothesis of an evolution of neuro-biological mechanism suggested by few authors isn't, actually, demonstrated. More probably, the modifications of lesional and, functional changes with disability observed are the consequence of elderly effects and decreasing of physical activites. We report a case of spinal cord compression by intramedullar tumor, associated with a post-polio syndrome.

[Atypical phenotype of Fabry disease. Evidence of a new mutation]. / Maladie de fabry à phénotype atypique. Mise en évidence d'une nouvelle mutation.

BACKGROUND: Fabry disease is a lysosomal disease resulting from deficient alpha galactosidase A activity. The enzyme's gene is situated on Xq22-1. Cardiac and cerebrovascular complications are usually observed late in the disease course. CASE REPORT: A 54-year-old patient was admitted for ischemic stroke subsequent to thrombosis of the right sylvian artery. The only significant event in the patient's history was hypertrophic cardiomyopathy that had progressed for 9 years. Search for an etiology identified alpha galacosidase A deficiency. Gene sequencing identified a new mutation. DISCUSSION: Two clinical forms of Fabry disease are described. The classical form has an early onset and is associated with systemic manifestations. The less common atypical form is associated with late-onset cardiomyopathy with no other systemic manifestations. Several mutations of the alpha galactosidase A gene have been recognized but to date no correlation has been established between the genotype and the phenotype. Our patient had an "intermediary" form of the disease associating a late onset, predominant cardiac manifestations, and limited systemic manifestations. The mutation observed in this case has not been described previously. Its relationship with the observed clinical phenotype remains to be demonstrated.

Cathepsin L gene organization in crustaceans.

The gene structure of a cathepsin L of the shrimp Penaeus vannamei has been determined by the polymerase chain reaction. It comprises six exons of various lengths spanning a total of 1792bp. This architecture is homologous to that of rat cathepsin L, three conserved sites of intron position have been effectively identified, with the exception of the third intron break-point located immediately after the cysteinyl active site. In contrast, no similarity is observed with Drosophila or Plasmodium cathepsin L-like gene organizations. This gene expresses a major cathepsin L enzyme in the hepatopancreas. The last intron is polymorphic, suggesting the presence of at least three different genes.

Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene.

Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development.

Cloning and expression of cathepsin L-like proteinases in the hepatopancreas of the shrimp Penaeus vannamei during the intermolt cycle.

Cysteine protease activities have been characterized with benzyloxycarbonyl-lysine p-nitrophenyl ester as a synthetic substrate and E64 as a specific inhibitor in the hepatopancreas of the shrimp Penaeus vannamei. An optimum pH of 5.1 has been measured. To characterize these cysteine proteases, a hepatopancreas cDNA library was screened by hybridization to a Norway lobster cysteine protease cDNA fragment. Two cDNAs encoding P. vannamei cysteine protease precursors have been cloned and sequenced. The encoded polypeptides have 326 and 322 amino acid residues, respectively, each consisting of partial signal sequences (15 and 10 residues), a pro-region (93 and 94 residues), and a mature enzyme polypeptide (218 residues). Cys25, His159 and Asn175 form the catalytic triad in the putative active site of the mature enzymes. Compared with invertebrate cysteine proteases (Homarus and Fasciola), each of the two shrimp enzymes shows 70 and 52% amino acid sequence identity, respectively; 63% identity is shown with rat cathepsin L. Northern hybridization analysis showed the same size for the different cysteine protease transcripts in hepatopancreas tissue (approximately 1.1 kb). During intermolt cycles, variations in cysteine protease activity were correlated with the variations in the levels of specific mRNA.

Molecular cloning and sequencing of two cDNAs encoding cathepsin L-related cysteine proteinases in the nervous system and in the stomach of the Norway lobster (Nephrops norvegicus).

Two cathepsin L-related cysteine proteinase molecular clones were isolated from cDNA libraries of mRNA from the eyestalk nervous system and the stomach of Nephrops norvegicus and sequenced. The cDNA from nervous system was first obtained by screening an eyestalk cDNA library with an oligonucleotide whose sequence derived from the amino acid sequence of a peptide isolated previously and subsequently with the 5' end of the longest cDNA probe thus obtained. Several clones were isolated and analysed: one of these clones contains the complete cDNA (NCP1:AC = X80989). It encodes a preproenzyme of 324 amino acid residues, and a putative mature enzyme of 217 residues. Only one variant (with one amino acid change) was identified. The screening of the stomach cDNA library was carried out with a cDNA probe corresponding to the 5' terminal region of the nervous system cysteine proteinase cDNA previously obtained. A near full-length cDNA (NCP2:AC = X80990) was isolated. The sequence for mature stomach cathepsin L-related cysteine proteinase is 215 residues long. Nervous system cathepsin L-like NCP1 is very similar to the American lobster cysteine proteinase LCP1 (81% identity) and the stomach cathepsin L-related NCP2 is very similar to cysteine protease LCP3 (82% identity). Moreover, comparison of the two Nephrops norvegicus cathepsin L-related cysteine proteinases revealed only 68% identity.

Surgery for parathyroid adenoma and hyperplasia: relationship of histology to outcome.

Recent histopathologic evidence challenges the teaching that enlargement of a solitary parathyroid gland is invariably caused by an adenoma, whereas multiple gland enlargement results from hyperplasia. We have re-examined the parathyroid tissue obtained from 152 consecutive patients undergoing surgery for primary hyperparathyroidism and compared it with their clinical outcome. Our approach was to excise enlarged glands and biopsy the remainder. In 124 patients (82%) at least three glands were biopsied or removed. The ratio of adenoma to hyperplasia was reversed by our histologic re-examination; adenomas were found in only 27 patients (25 single, two double), whereas hyperplasia was found in 117 patients (one gland, 87 patients; two glands, 16 patients; three glands, five patients; four glands, nine patients). Normal tissue only was reported in eight patients. During a 2-year follow-up, five patients (3%) developed hypocalcemia and none developed recurrent hypercalcemia. Our results indicate that a full neck exploration with removal of all enlarged glands is more important than the histologic diagnosis in planning a successful surgical strategy for primary hyperparathyroidism.

Benign epithelial neoplasms of the appendix: classification and clinical associations.

The nomenclature of non-carcinoid epithelial proliferations of the appendix is confused and many of the terms used have no histogenetic basis. A classification based on the well-established diagnostic categories of colonic epithelial polyps has been proposed recently. We have applied this classification to 42 benign epithelial lesions of the appendix in order to determine its suitability for routine diagnostic use, and in order to determine the prognosis of patients with these lesions. All lesions could be classified as either hyperplastic, adenomatous, mixed hyperplastic/adenomatous or dilated appendices. Six cases were associated with a synchronous carcinoma of the colon with all types of appendiceal histology being represented. Follow-up of the remainder of the patients revealed two subsequent colonic carcinomas, at 3 and 6 years post-appendicectomy respectively. In both of these patients, the appendix had shown adenomatous epithelium. We suggest that adenomas of the appendix may have a similar prognostic significance to adenomas elsewhere in the large bowel.

Alpha-smooth muscle actin as a marker for soft tissue tumours: a comparison with desmin.

The immunoreactivity of a range of vascular and non-vascular smooth muscle tumours, rhabdomyosarcomas, and non-myoid lesions has been examined with the use of a monoclonal antibody to smooth muscle-specific actin and the muscle intermediate filament, desmin. In all cases of smooth muscle-derived tumours, the alpha-actin antibody yielded superior results. Staining of the myofibroblasts of fibromatoses was also seen. In contrast to desmin, immunoreactivity was not exhibited by rhabdomyosarcomas. We propose that this monoclonal antibody to alpha-smooth muscle actin is a useful addition to the panel of reagents used for the characterization of soft tissue proliferations and tumours. The technical aspects of the application of this monoclonal antibody to immunohistochemistry are discussed.

A case of ovarian fibromatosis with disseminated intra-abdominal fibromatosis.

A case of bilateral ovarian fibromatosis and massive oedema with subsequent intra-abdominal fibromatosis which underwent an aggressive and fatal course is described. This is the first report of co-existence of these two conditions and the possible relationship between them is discussed.

Induction of hypoxia in normal and malignant tissues by changing the oxygen affinity of hemoglobin--implications for therapy.

The drug BW12C, which increases the oxygen affinity of hemoglobin, reduces oxygen availability to tissues. This results in protection against radiation damage to the hemopoietic system and epidermal Langerhans cells in CBA mice. The drug also protects against beta-irradiation damage in pig epidermis. BW12C increases the hypoxic cell fraction in tumors and histological examination of an experimental T cell lymphoma shows that the induced hypoxia leads to tumor necrosis.