Hipotonía neonatal: ¿entraña un diagnóstico difícil? / Neonatal hypotonia: is it a diagnostic challenge?

Introducción. La hipotonía constituye un signo habitual de enfermedad en el neonato. Ahora bien, se trata de un signo inespecífico: puede ser la manifestación inicial de una enfermedad neurológica o multisistémica. Objetivos. Estudiar las principales causas de la hipotonía neonatal y evaluar la exactitud diagnóstica de la anamnesis y la exploración física en el neonato hipotónico. Pacientes y métodos. Estudio retrospectivo de 22 años con recién nacidos afectados por hipotonía e ingresados en la unidad de cuidados intensivos neonatales. A partir de la anamnesis y de los datos recabados durante la exploración física, se hizo una clasificación inicial en condiciones de enmascaramiento del tipo de hipotonía: central, periférica o indeterminada. Resultados. El número de pacientes estudiados ascendió a 91. De ellos, 42 (46,2%) presentaban antecedentes de alteraciones prenatales: polihidramnios (28,6%), retraso del crecimiento intrauterino (21,4%) y presentación de nalgas (19%). Cincuenta y tres (58,2%) habían precisado reanimación al nacer. Los principales síntomas asociados consistieron en disnea (65,9%), dificultades de alimentación (36,5%) y escasez de movimientos espontáneos (22,4%). El diagnóstico definitivo se obtuvo en 64 neonatos (70,3%): el 81,3% mostraba hipotonía central, y el 18,7%, hipotonía periférica. El valor predictivo positivo de la clasificación inicial alcanzó el 97,9% en la hipotonía central y el 66,7% en la hipotonía periférica. La tasa de mortalidad fue del 8,8%, y resultó superior en el grupo de hipotonía periférica (58,3% frente a 1,3%). Conclusiones. La hipotonía neonatal aparece vinculada con una larga lista de trastornos. Una anamnesis minuciosa y una valoración neurológica cuidadosa brindan un alto valor predictivo diagnóstico que debe orientar el estudio etiológico

Introduction. Hypotonia is a frequent sign of disease in newborns. However, it's a nonspecific clinical finding: may be the presentation form of a systemic or neurological disease. Aims. To study the main causes of neonatal hypotonia as well as to evaluate the diagnostic accuracy of the anamnesis and physical examination of the hypotonic newborn. Patients and methods. A 22-year retrospective study of hypotonic neonates admitted to the Neonatal Intensive Care Unit was conducted. It was performed an initial blind classification of hypotonia’s type (central-CH, peripheral-PH or undetermined hypotonia) based on the clinical history and the recorded data of physical examination. Results. 91 infants were included. 42 (46.2%) had prenatal history abnormalities: polyhydramnios (28.6%), intrauterine growth restriction (21.4%) and pelvic presentation (19.0%). 53 (58.2%) required resuscitation at birth. The main associated symptoms were respiratory distress (65.9%), feeding difficulties (36.5%) and decreased spontaneous movements (22.4%). The final diagnosis was reached in 64 newborns (70.3%): 81.3% with CH, 18.7% with PH. The positive predictive value of the initial classification was 97.9% in CH and 66.7% in PH group. The mortality rate was 8.8% and it was higher in PH group (58.3% vs 1.3%). Conclusions. Neonatal hypotonia can be associated to an extensive list of disorders. A detailed clinical history associated to a careful neurological evaluation present a high diagnostic predictive value that should guide the etiological investigation

Avaliação Biodinâmica dos Músculos Temporal e Masseter em Indivíduos com Síndrome de Down / Biodynamic evaluation of the temporal and masseter muscles in individuals with down's syndrome

A Síndrome de Down (SD), também conhecida Trissomia do 21, é uma anomalia cromossômica, referente a presença de um cromossomo 21 extranumerário, decorrente de uma duplicação do mesmo. Descrita no século XIX, a SD é caracterizada por particularidades fenotípicas e morfológicas, tais como: cardiopatias congênitas, deficiências neuromotoras, clinodactilia do 5º dedo das mãos, presença de prega palmar única, aumento da distância entre o 1º e o 2º artelhos nos pés, dentre outras. Em relação às características orofaciais, esses indivíduos têm frequentemente expressão facial sindrômica, pálpebras oblíquas craniolateral, língua protruída repousando sobre os incisivos inferiores (pseudomacroglossia), salivação aumentada, maxilar hipoplásico e protrusão mandibular. Outra condição é a hipotonia muscular generalizada, resultando em uma sinergia muscular prejudicada. Isto pode desencadear disfunção mastigatória, desordem na fala e disfagia. Portanto, o objetivo desta pesquisa foi realizar um estudo comparativo dos padrões eletromiográficos dos músculos mastigatórios masseter direito e esquerdo (porção superficial); e temporal direito e esquerdo (porção anterior); por meio da eletromiografia de superfície, em indivíduos com SD. A atividade muscular foi avaliada quando os músculos mastigatórios estavam nos estados de repouso (REP), Contração Máxima Voluntária (CMV), Máxima Intercuspidação Habitual (MIH) e também dados obtidos por meio da Força Mandibular Total (FMT), sendo comparada com os registros de uma amostra controle formada por indivíduos sem deficiência. Assim, 34 indivíduos adultos jovens, sem distinção de gênero foram selecionados aleatoriamente e divididos em 2 grupos: 24 indivíduos com Síndrome de Down (Grupo SD) e 10 indivíduos normais (Grupo Controle). Os dados foram submetidos à análise estatística, expressos em média ± desvio-padrão e, para comparação dos parâmetros, foram utilizados o teste de Mann-Whitney e análise da Correlação de Pearson (r). Os resultados demonstraram menor atividade elétrica nos músculos estudados do grupo SD. Na análise de Correlação observou-se que as relações unilaterais em REP e MIH nos indivíduos com SD com valores menores e insignificantes encontram-se mais comprometidas, bem como as relações interlaterais desses pacientes em REP, isto não acontecendo nos indivíduos normais do grupo controle, onde suas correlações podem ser consideradas de média e alta intensidade. Portanto, na biodinâmica de ambos os músculos, temporal e masseter, evidenciamos uma menor participação na ação muscular nos indivíduos com SD(AU)

Down Syndrome (SD), also known as Trisomy 21, is a chromosomal anomaly, referring to the presence of a supernumerary chromosome 21, due to a duplication of the same. Described in the 19th century, SD is characterized by phenotypic and morphological features such as: congenital heart defects, neuromotor deficiencies, clinodactyly of the 5th finger, presence of a single palmar fold, increased distance between the 1st and 2nd toes on the feet, among others. Regarding orofacial characteristics, these individuals often have syndromic facial expression, craniolateral oblique eyelids, protruding tongue resting on the lower incisors (pseudomacroglossia), increased salivation, hypoplastic maxillary and mandibular protrusion. Another condition is generalized muscle hypotonia, resulting in impaired muscle synergy. This can trigger masticatory dysfunction, speech disorder and dysphagia. Therefore, the objective of this research was to perform a comparative study of the electromyographic patterns of the right and left masseter masticatory muscles (superficial portion); and right and left temporal (anterior portion); by means of surface electromyography, in individuals with DS. Muscle activity was assessed when the masticatory muscles were in rest states (REP), Maximum Voluntary Contraction (CMV), Maximum Habitual Intercuspation (MIH) and also data obtained through Total Mandibular Force (FMT), compared to the records of a control sample formed by individuals without disability. Thus, 34 young adult individuals, without gender distinction were randomly selected and divided into 2 groups: 24 individuals with Down Syndrome (SD Group) and 10 normal individuals (Control Group). The data were submitted to statistical analysis, expressed as mean ± standard deviation, and the Mann-Whitney test and Pearson's correlation (r) were used to compare the parameters. The results showed lower electrical activity in the muscles studied in the SD group. In the correlation analysis it was observed that the unilateral relationships in REP and MIH in the individuals with SD with smaller and insignificant values are more compromised, as well as the interlateral relationships of these patients in REP, this not happening in the normal individuals of the control group, where its correlations can be considered medium and high intensity. Therefore, in the biodynamics of both muscles, temporal and masseter, we evidenced a smaller participation in the muscular action in the individuals with SD(AU)

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BACKGROUND: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits. METHODS: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations. RESULTS: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population. CONCLUSION: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup.

Síndrome hipotónico del lactante / Hypotonic syndrome in the newborn infant

Entendemos como hipotonía la disminución acentuada del tono muscular que afecta al desarrollo motor normal y que puede afectar a la musculatura axial y de los miembros y, en ocasiones, a la facial. Es un cuadro que genera un gran desafío ya que, en su universo, comprende una serie bastante amplia de condiciones que afectan a distintas áreas del sistema nervioso, tanto central como periférico, y que pueden ser expresión de patologías de corte benigno o de pronóstico reservado. Abarcan miopatías, alteraciones metabólicas, enfermedades de corte genético, endocrinopatías y enfermedades progresivas o crónicas, entre otras causas. El gran desarrollo de la medicina actual ha logrado poner a disposición del examinador múltiples herramientas que permiten afinar o aseverar el diagnóstico, entre las que destacan los desarrollos logrados en las investigaciones genéticas, así como los estudios de imágenes y de microscopía óptica y electrónica. Sin embargo, pese a toda esta oferta, sigue siendo la clínica la que permite usar racionalmente estos avances y orientar hacia la posible etiología, localización topográfica y control evolutivo. Es de utilidad, para el enfoque diagnóstico y la utilización de métodos auxiliares, que la localización topográfica de la afectación ya esté ésta ubicada en el cerebro, el cerebelo, el tallo, la médula, los nervios periféricos, la unión mioneural o el músculo (AU)

Hypotonia is understood to refer to a pronounced decrease in muscle tone that affects normal motor development and that may affect the axial muscles as well as those of the limbs and, sometimes, the face. It is a very challenging clinical picture because it consists in a fairly wide range of conditions that affect different areas of the central and peripheral nervous system and may be the expression of pathologies that can be either benign or of an uncertain prognosis. These cover myopathies, metabolic disorders, diseases based on genetic causes, pathologies affecting the endocrine glands and progressive or chronic diseases, among other aetiologies. The important development of medicine today has made a number of tools available to the examiner with which to refine or pronounce a diagnosis. Such instruments include the developments achieved in genetic research, together with studies conducted in imaging and optical and electronic microscopy. However, in spite of having all this material available for use, it is still the clinical features that allow a rational use to be made of these advances to be able to point towards the possible causation, topographic location and developmental control. It is useful, for the diagnostic approach and the use of auxiliary methods, to know the topographic location of the disorder, whether it is situated in the brain, the cerebellum, the stem, the spinal cord, the peripheral nerves, the myoneural junction or the muscle (AU)

[Hypotonic syndrome in the newborn infant]. / Síndrome hipotónico del lactante.

Hypotonia is understood to refer to a pronounced decrease in muscle tone that affects normal motor development and that may affect the axial muscles as well as those of the limbs and, sometimes, the face. It is a very challenging clinical picture because it consists in a fairly wide range of conditions that affect different areas of the central and peripheral nervous system and may be the expression of pathologies that can be either benign or of an uncertain prognosis. These cover myopathies, metabolic disorders, diseases based on genetic causes, pathologies affecting the endocrine glands and progressive or chronic diseases, among other aetiologies. The important development of medicine today has made a number of tools available to the examiner with which to refine or pronounce a diagnosis. Such instruments include the developments achieved in genetic research, together with studies conducted in imaging and optical and electronic microscopy. However, in spite of having all this material available for use, it is still the clinical features that allow a rational use to be made of these advances to be able to point towards the possible causation, topographic location and developmental control. It is useful, for the diagnostic approach and the use of auxiliary methods, to know the topographic location of the disorder, whether it is situated in the brain, the cerebellum, the stem, the spinal cord, the peripheral nerves, the myoneural junction or the muscle.

TITLE: Sindrome hipotonico del lactante.Entendemos como hipotonia la disminucion acentuada del tono muscular que afecta al desarrollo motor normal y que puede afectar a la musculatura axial y de los miembros y, en ocasiones, a la facial. Es un cuadro que genera un gran desafio ya que, en su universo, comprende una serie bastante amplia de condiciones que afectan a distintas areas del sistema nervioso, tanto central como periferico, y que pueden ser expresion de patologias de corte benigno o de pronostico reservado. Abarcan miopatias, alteraciones metabolicas, enfermedades de corte genetico, endocrinopatias y enfermedades progresivas o cronicas, entre otras causas. El gran desarrollo de la medicina actual ha logrado poner a disposicion del examinador multiples herramientas que permiten afinar o aseverar el diagnostico, entre las que destacan los desarrollos logrados en las investigaciones geneticas, asi como los estudios de imagenes y de microscopia optica y electronica. Sin embargo, pese a toda esta oferta, sigue siendo la clinica la que permite usar racionalmente estos avances y orientar hacia la posible etiologia, localizacion topografica y control evolutivo. Es de utilidad, para el enfoque diagnostico y la utilizacion de metodos auxiliares, que la localizacion topografica de la afectacion ya este esta ubicada en el cerebro, el cerebelo, el tallo, la medula, los nervios perifericos, la union mioneural o el musculo.

Genetic evaluation of the pediatric patient with hypotonia: perspective from a hypotonia specialty clinic and review of the literature.

AIM: Hypotonia is a symptom of diminished tone of skeletal muscle associated with decreased resistance of muscles to passive stretching, which can be caused by abnormalities of the central nervous system, any element of the lower motoneuron, or both. Hypotonia is not a specific diagnosis, but can be part of over 500 different genetic disorders, with many other conditions waiting to be identified. This review proposes a pragmatic approach to evaluating hypotonia in neonatal and pediatric populations by using a diagnostic algorithm. METHOD: We use a dedicated literature review combined with clinical experience in a newly established multidisciplinary center for hypotonia to establish a diagnostic algorithm. RESULTS: Hypotonia can be a symptom of over 500 different genetic disorders. It can present as peripheral, central, or combined hypotonia, providing necessity for rational and systematic diagnostic testing. INTERPRETATION: Our analyses demonstrate that a staged diagnostic approach categorizing patients as having peripheral, central, or combined hypotonia is the most efficient to providing a rational work-up. Establishing a diagnosis is crucial for prognosis, management, and treatment strategies, and for ascertaining an accurate recurrence risk for future offspring in a family.

Clinical characteristics of hypotonia: a survey of pediatric physical and occupational therapists.

PURPOSE: This study extended previous work on defining characteristics of children with hypotonia. METHODS: A survey regarding previously identified characteristics of hypotonia, examination tools, interventions, and prognosis was sent to a random sample of 500 physical therapists and 500 occupational therapists. RESULTS: A total of 268 surveys were returned, for a response rate of 26.8%. Characteristics most frequently observed in children with hypotonia included decreased strength, hypermobile joints, and increased flexibility. Observation was the most commonly cited assessment tool and 85% of those surveyed believe that characteristics of hypotonia improve with therapy. CONCLUSIONS: Despite agreement among physical and occupational therapists on characteristics of hypotonia and potential for improvement, clear clinical guidelines for the diagnosis and quantification of hypotonia have yet to be determined. Research is needed to develop an operational definition of hypotonia, develop valid tests and assess effectiveness of intervention.

Hip displacement in cerebral palsy.

BACKGROUND: Hip displacement is considered to be common in children with cerebral palsy but the reported incidence and the proposed risk factors vary widely. Knowledge regarding its overall incidence and associated risk factors can facilitate treatment of these children. METHODS: An inception cohort was generated from the Victorian Cerebral Palsy Register for the birth years 1990 through 1992, inclusive, and multiple data sources pertaining to the cohort were reviewed during 2004. Gross motor function was assessed for each child and was graded according to the Gross Motor Function Classification System (GMFCS), which is a valid, reliable, five-level ordinal grading system. Hip displacement, defined as a migration percentage of >30%, was measured on an anteroposterior radiograph of the pelvis with use of a reliable technique. RESULTS: A full data set was obtained for 323 (86%) of 374 children in the Register for the birth years 1990 through 1992. The mean duration of follow-up was eleven years and eight months. The incidence of hip displacement for the entire birth cohort was 35%, and it showed a linear relationship with the level of gross motor function. The incidence of hip displacement was 0% for children with GMFCS level I and 90% for those with GMFCS level V. Compared with children with GMFCS level II, those with levels III, IV, and V had significantly higher relative risks of hip displacement (2.7, 4.6, and 5.9, respectively). CONCLUSIONS: Hip displacement is common in children with cerebral palsy, with an overall incidence of 35% found in this study. The risk of hip displacement is directly related to gross motor function as graded with the Gross Motor Function Classification System. This information may be important when assessing the risk of hip displacement for an individual child who has cerebral palsy, for counseling parents, and in the design of screening programs and resource allocation.

Characteristics of hypotonia in children: a consensus opinion of pediatric occupational and physical therapists.

PURPOSE: The term hypotonia is often used to describe children with reduced muscle tone, yet it remains abstract and undefined. The purpose of this study was to identify characteristics of children with hypotonia to begin the process of developing an operational definition of hypotonia. METHODS: Three hundred physical and occupational therapists were systematically selected from the memberships of the Pediatric Section of the American Physical Therapy Association and the Developmental Delay Section of the American Occupational Therapy Association and asked to complete an open-ended survey exploring characteristics of strength, endurance, mobility, posture, and flexibility. RESULTS: The response rate was 26.6%. Forty-six physical therapists and 34 occupational therapists participated. The criterion for consensus about a characteristic was being mentioned by at least 25% of respondents from each discipline. The consensus was that children with hypotonia have decreased strength, decreased activity tolerance, delayed motor skills development, rounded shoulder posture, with leaning onto supports, hypermobile joints, increased flexibility, and poor attention and motivation. CONCLUSION: An objective tool for defining and quantifying hypotonia does not exist. A preliminary characterization of children with hypotonia was established, but further research is needed to achieve objectivity and clarity.

[Pathophysiology of urge, stress, and mixed incontinence]. / Pathophysiologie von Drang-, Belastungs- und Mischinkontinenz.

According to the new ICS classification, urinary incontinence is subdivided by symptomatic, clinical, and urodynamic criteria. Understanding the pathophysiological interactions is important to find the correct diagnosis. Disturbances in bladder storage include urge incontinence due to neurogenic or non-neurogenic (idiopathic) detrusor hyperactivity as well as stress urinary incontinence caused by an insufficient urethral closure mechanism due to reduced pressure transmission (active-passive), hypotonic urethra, hyporeactivity of sphincter musculature, or involuntary relaxation of the urethra. Stress and urge incontinence can occur in combination and then be defined as mixed incontinence.

Congenital fiber type disproportion--30 years on.

Thirty years ago, M. H. Brooke coined the term "congenital fiber type disproportion" (CFTD) to describe 12 children who had clinical features of a congenital myopathy and relative type 1 fiber hypotrophy on muscle biopsy. It is now clear that this histological pattern can accompany a wide range of neurological disorders, leading to disillusionment with CFTD as a distinct nosological entity. To determine whether the CFTD has clinical utility as a diagnostic entity, we have reviewed the literature for cases of type 1 fiber hypotrophy and have used strict exclusion criteria to identify 67 cases of CFTD. Most patients presented at birth with weakness and hypotonia, had normal intelligence, and followed a static or improving clinical course. In 43% of families, more than 1 individual was affected. Failure to thrive was common and 25% of patients had contractures or spinal deformities. Bulbar weakness and ophthalmoplegia were less common and cardiac involvement was rare. Twenty-five percent followed a severe course and 10% had died at the time of reporting, all from respiratory failure. Ophthalmoplegia and facial and bulbar weakness were significantly associated with a poorer prognosis. The relatively homogeneous phenotype supports the retention of CFTD as a distinct diagnostic entity and familial occurrence suggests a genetic basis. Regarding the diagnosis of CFTD, we found no strong evidence that the minimum difference between type 1 and type 2 fiber sizes should be increased from 12% to 25%. We also list the other reported causes of relative type 1 fiber hypotrophy to aid their exclusion from CFTD.

Diagnostic profile of neonatal hypotonia: an 11-year study.

The profile of disorders presenting with neonatal hypotonia to the neonatal intensive care unit has not been studied previously. An 11-year retrospective cohort study of neonates, who were identified through computer database records and were admitted to the Neonatal Intensive Care Unit from January 1989 to December 1999 at the Montreal Children's Hospital (Montreal, Québec), is presented. The final diagnoses, tests obtained, and outcome were determined from a structured review of the subject's hospital record. The database search generated 95 records, of which 50 neonates met the inclusion criteria. The hypotonia was classified as central in 33 patients (66%) and peripheral in 17 (34%). Hypoxic-ischemic encephalopathy (n = 13), Prader-Willi syndrome (n = 6), myotonic dystrophy (n = 6), other muscle disorders (n = 6), chromosomal disorders (n = 4), and peripheral nerve disorders (n = 3) were the most common diagnoses. The genetic tests of highest yield were fluorescent in situ hybridization for Prader-Willi syndrome, DNA methylation studies for Prader-Willi syndrome, trinucleotide repeat testing for myotonic dystrophy, and karyotype analysis. A diagnostic approach is proposed based on the results.

[Types of disorders of the contractile function of the heart in acute myocardial infarct]. / O tipakh narusheniia sokratitel'noi funktsii serdtsa pri ostrom infarkte miokarda.

Acute myocardial infarction is characterized by reduced contractile activity of the heart, which is manifested by pathological shifts in the phase structure of the left ventricular systole and parameters of hemodynamics corresponding to the syndrome of hypodynamia. The severity of the hypodynamia syndrome depends on the volume of the affected myocardium. On the basis of the degree of pathological shifts in the phase and hemodynamic indices, the authors distinguished several types of impaired cardiac contractility. In the course of stage-by-stage treatment applied on the principles of early activation, mobilization, and rehabilitation of patients, the dynamics differs with the type of the contractility disorder. In type I positive dynamics is revealed beginning with stage I, in type II beginning with stage II of treatment; in type III negative dynamics is noted in the early periods of the disease and positive dynamics in stage III of treatment. The differentiation of these types becomes very important in appraising the tactics, the prognosis, and the outcome of the disease. Close correlative relations were revealed between the phase indices and the indices of hemodynamics which allow more objective appraisal of the state of cardiac contractility in the acute period of myocardial infarction.