Posteromedial Hypothalamic Deep Brain Stimulation for Refractory Aggressiveness in a Patient With Weaver Syndrome: Clinical, Technical Report and Operative Video.

BACKGROUND AND IMPORTANCE: Deep brain stimulation of the posteromedial hypothalamus (PMH DBS) appears to be an effective treatment for drug-resistant aggressiveness. Weaver syndrome (WS) is a rare genetic disorder in which patients develop some degree of intellectual disability and rarely severe behavioral alterations that may benefit from this procedure. CLINICAL PRESENTATION: We present the case of a 26-yr-old man diagnosed with WS presenting with uncontrollable self and heteroaggressiveness and disruptive behavior refractory to pharmacological treatment and under severe physical and mechanical restraining measures. The patient was successfully treated with bilateral PMH DBS resulting in affective improvement, greater tolerance for signs of affection, regularization in his sleep pattern and appetite disturbances at 12-mo follow-up. A detailed description and video of the procedure are presented, and a review of the clinical characteristics of WS and the utility and benefits of PMH DBS for refractory aggressiveness are reviewed. CONCLUSION: To our knowledge, this is the first case of refractory aggressiveness described in WS as well as the first patient with WS successfully treated with PMH DBS.

Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity.

Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation ("handshake"), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.

Novel Technique for Toe-to-Hand Transplantation: The Fourth-toe as an Alternative Option for Toe-to-Hand Transplantation for Pediatric Patients.

The first toe-to-hand transplantation was done in 1898 by Nicoladoni. It was a staged procedure and the toe flap was based on a pedicle. With advancement of optical instruments and microsurgeons' skills in 1964 the first microvascular toe-to-hand transplantation on a rhesus monkey was done. The technique's development has not stopped, many authors have modified it to achieve better outcomes for both traumatic and congenital hand defects. The most commonly used toes for transplantation are first, second, and second to third toe block. Well described plantar and dorsal vascular systems for first web space vessels as well as possibility to perform successful perforator anastomosis allows us to improve toe-to-hand transplantation further. There is a paucity of studies on single fourth toe-to-hand transplantation. We performed fourth-toe transplantation for three pediatric patients (mean age, 73 mo) with congenital (n=2) and traumatic (n=1) hand defects. Common plantar digital arteries were used for blood supply to the transplanted toes. No vascular problems occurred, and all transplanted toes survived. Patients and parents are satisfied with functional and esthetic outcomes. Early podometry results show insignificant changes which should not harm the foot in the long-term. We believe the fourth-toe transplantation is a promising method to use to reconstruct congenital or traumatic absence of digits for pediatric population.

Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture.

Cortical development is a complex process where a multitude of factors, including cadherins, plays an important role and where disruptions are known to have far reaching effects in neural development and cortical patterning. Cadherins play a central role in structural left-right differentiation during brain and body development, but their effect on a functional level remains elusive. We addressed this question by examining functional cerebral asymmetries in a patient with Van Maldergem Syndrome (VMS) (MIM#601390), which is caused by mutations in DCHS1-FAT4 cadherins, using a dichotic listening task. Using neurophysiological (EEG) data, we show that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. Basic perceptual processing of biaurally presented auditory stimuli was unaffected. This suggests that the strength and emergence of functional cerebral asymmetries is a direct function of proliferation and differentiation of neuronal stem cells. Moreover, these results support the recent assumption that the molecular mechanisms establishing early left-right differentiation are an important factor in the ontogenesis of functional lateralization.

Soft-Tissue Surgery for Camptodactyly Corrects Skeletal Changes.

BACKGROUND: This study demonstrates the potential for radiographic and clinical improvement with surgical correction of camptodactyly. Although historically these radiographic changes have been held to be permanent, the authors encourage surgical intervention for digits with severe flexion contracture or progressive radiographic changes before skeletal maturity is reached. METHODS: The authors assessed 18 consecutively operated fingers in nine skeletally immature patients in whom advanced radiographic articular changes had occurred. Mean preoperative flexion contracture was 63 degrees (range, 35 to 105 degrees). The average age of the patients was 11 years (range, 4 to 15 years) at the time of surgery. Clinical response to surgery was studied, but radiographic articular changes were followed postoperatively as a primary outcome. RESULTS: Each patient demonstrated the classic preoperative radiographic joint changes on radiographic films at the affected proximal interphalangeal or distal interphalangeal joint. All patients had substantial clinical improvement postoperatively. Two digits had extensive radiographic damage, requiring proximal interphalangeal joint arthrodesis. Fifteen of the remaining 16 digits (94 percent) had substantial improvement or full restoration of radiographic articular congruency at average follow-up of 9 months (range, 3 to 18 months). The only joint that did not remodel fully was the one that did not have complete clinical correction. CONCLUSIONS: Even in patients with severe radiographic changes from camptodactyly, surgery can effectively improve range of motion. Once radiographic articular changes become apparent, surgical correction should be undertaken not only to prevent further joint damage but also to reverse these radiographic changes before skeletal maturity is reached. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Radiologic findings of Patterson-Lowry rhizomelic dysplasia in two sisters.

We report two sisters who have a rare skeletal abnormality termed Patterson-Lowry rhizomelic dysplasia. The typical findings of these cases on bone survey are isolated shortening and proximal metaphyseal enlargement and cupping of the bilateral humeri. The elder sister also has coxa vara deformity and dysplastic proximal femoral epiphyses on both sides. The younger sister has normal hip joint bones bilaterally, but her proximal femoral epiphyses are smaller than normal. All other bones of the sisters are of normal size and configuration. Our patients are two siblings, and their parents are first degree relatives, suggesting autosomal-recessive (AR) inheritance. The present patients help us to understand the genetic relationships and skeletal variabilities of this rare entity.

Superimposed electrical stimulation improves mobility of pre-stiff thumbs after ulnar collateral ligament injury of the metacarpophalangeal joint: a randomized study.

OBJECTIVE: This study aimed at testing the ability of the superimposed electrical stimulation technique to restore the mobility of pre-stiff thumbs after operative repair for rupture of the ulnar collateral ligament. MATERIAL AND METHODS: Eight patients demonstrating a pre-stiff metacarpophalangeal joint were involved in two rehabilitation sessions of a counterbalanced design. In the voluntary contraction session, they performed 20min of repeated active flexions of the impaired metacarpophalangeal joint. In the superimposed electrical stimulation session, they performed 20min of percutaneous neuromuscular electrical stimulations which were superimposed to voluntary flexion. RESULTS: Mean active range of motion improvement from pre- to post-session was significantly greater in the superimposed electrical stimulation condition compared to the voluntary contraction condition (11±5 deg versus 3±4 deg; P<0.01). CONCLUSION: Superimposing electrical stimulation to voluntary contractions is an efficient technique to improve active range of motion of the pre-stiff metacarpophalangeal joint of the thumb.

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

BACKGROUND AND OBJECTIVES: Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. METHODS: The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. RESULTS: We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described. CONCLUSIONS: Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.

Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling.

Altered Bone Morphogenetic Protein (BMP) signaling leads to multiple developmental defects, including brachydactyly and deafness. Here we identify chondroitin synthase 1 (CHSY1) as a potential mediator of BMP effects. We show that loss of human CHSY1 function causes autosomal-recessive Temtamy preaxial brachydactyly syndrome (TPBS), mainly characterized by limb malformations, short stature, and hearing loss. After mapping the TPBS locus to chromosome 15q26-qterm, we identified causative mutations in five consanguineous TPBS families. In zebrafish, antisense-mediated chsy1 knockdown causes defects in multiple developmental processes, some of which are likely to also be causative in the etiology of TPBS. In the inner ears of zebrafish larvae, chsy1 is expressed similarly to the BMP inhibitor dan and in a complementary fashion to bmp2b. Furthermore, unrestricted Bmp2b signaling or loss of Dan activity leads to reduced chsy1 expression and, during epithelial morphogenesis, defects similar to those that occur upon Chsy1 inactivation, indicating that Bmp signaling affects inner-ear development by repressing chsy1. In addition, we obtained strikingly similar zebrafish phenotypes after chsy1 overexpression, which might explain why, in humans, brachydactyly can be caused by mutations leading either to loss or to gain of BMP signaling.

Cobertura de defectos amplios de la mano con colgajo inguinal. A propósito de un caso / Coverage of large hand defects with inguinal flap. A case report

Se presenta el caso de un defecto amplio de cobertura de la mano en un varón de 53 años, con lesión asociada por cizallamiento, que desaconsejaba el uso de colgajos de proximidad. Se consiguió la cobertura con un colgajo inguinal adelgazado obteniendo una buena adaptación y aspecto estético (AU)

We present the case of a 53 years-old man with a large defect of the hand associated with degloving injury that did not advise us to use local flaps. We obtained coverage with a thin inguinal flap achieving a good adaptation and aesthetic appearance (AU)

Formative research to develop and test messages to educate mothers on zinc supplementation in childhood diarrhea

BACKGROUND: Zinc is now recommended as part of childhood diarrhea case management but there are concerns regarding treatment duration and perceptions of its use when given with ORT. OBJECTIVES: This study developed and tested messages on zinc supplementation for childhood diarrhea. METHODS: Messages were based on 1) a review of literature and product advertisements, 2) drugstore seller interviews, and 3) focus group discussions (FGDs) among 10 mothers with children six to 59 months old. Subsequent FGDs with 15 mothers consulting at a government hospital helped determine message clarity, comprehension and appeal. A behavioral trial, involving nine mothers whose children had diarrhea, tested recall of and adherence to the messages. RESULTS: The trial tested three messages - zinc: 1) strengthens resistance; 2) is a vitamin for the gut; 3) increases the appetite of a child with diarrhea. Seven of nine mothers were able to follow instructions on zinc administration, and demonstrated recall and understanding of these messages. Mothers understood that zinc helps the child with diarrhea, improves appetite, reduces symptoms and hastens recovery, but had concerns regarding the side effects (vomiting), co-morbidities (fever, cough) and consequences of overdose. Standardized counseling cards addressed these concerns. Respondents preferred a simple logo labeled with zinc administration instructions on the packaging. Zinc supplementation did not affect ORT use. CONCLUSION AND RECOMMENDATIONS: Messages sufficiently addressed mothers concerns on zinc use during childhood diarrhea, with those on zinc improving and as a vitamin for the gu having the best recall. Results can contribute to introduction and promotion in the public sector.

Mental rotation of congenitally absent hands.

We compared motor imagery performance of normally limbed individuals with that of individuals with one or both hands missing since birth (i.e., hand amelia). To this aim, 14 unilaterally and 2 bilaterally amelic participants performed a task requiring the classification of hands depicted in different degrees of rotation as either a left or a right hand. On the same task, 24 normally limbed participants recapitulated previously reported effects; that is, that the hand motor dominance and, more generally, a lifelong use of hands are important determinants of left-right decisions. Unilaterally amelic participants responded slower to hands corresponding to their absent, compared with their existing, hand. Moreover, left and right hand amelic participants showed prolonged reaction times to hands (whether left or right) depicted in unnatural orientations compared with natural orientations. Among the bilateral amelics, the individual with phantom sensations, but not the one without, showed similar differentiation. These findings demonstrate that the visual recognition of a hand never physically developed is prolonged, but still modulated by different rotation angles. They are further compatible with the view that phantom limbs in hand amelia may constrain motor imagery as much as do amputation phantoms.

Long-term complications of iris-claw phakic intraocular lens implantation in Weill-Marchesani syndrome.

PURPOSE: This study was designed to report the long-term complications of iris-claw phakic intraocular lens implantation in a patient with Weill-Marchesani syndrome. METHODS: Case report and literature review. RESULTS: A 26-year-old man with a history of glaucoma had bilateral phakic lens implantation for high myopia 10 years previously. Two years later, the left implant dislocated and was repositioned. Slit-lamp examination of both eyes revealed phakic implants of the iris-claw variety. There were moderate iridocorneal adhesions in the areas in which the lens haptics pinched the iris in both eyes and moderate epithelial and stromal edema over the temporal one-third of the left cornea. The crystalline lenses were clear with 3+phacodonesis OU. Dilated fundus examinations revealed bilateral severe optic nerve cupping. Crystalline lens diameters were measured at 7.5mm in the right eye and 8 mm in the left. Anterior chamber depths were 2.63 mm OD and 2.40 mm OS. Specular microscopy revealed central endothelial cell counts of 1133 and 587 cells/mm OD and OS, respectively. Axial lengths were 23.3 mm OD and 25 mm OS. Gonioscopic examination revealed bilateral angle closure with marked peripheral anterior synechiae. Based on our findings of short stature, shortened and thickened fingers, relatively normal axial length, microspherophakia, high myopia, and glaucoma, we diagnosed the patient with Weill-Marchesani syndrome. CONCLUSION: Iris claw-lens phakic lenses may be an effective surgical alternative to correct high myopia in select patients; however, it may produce long-term complications in eyes with specific features.

A further case of opsismodysplasia with hydrocephalus.

We present a case of opsismodysplasia, a very rare skeletal dysplasia, in a term newborn female who had short length, short extremities and markedly short fingers. Radiological studies demonstrated severe platyspondyly, absence of epiphyseal ossification centers, short tubular bones, especially severe in hands and feet, with metaphyseal cupping. She also had hydrocephaly, a rare finding in opsismodysplasia. In our literature review we have found 24 cases, 17 born alive and seven terminations of pregnancy (TOPs).

Freeman-Sheldon syndrome: dental and orthodontic implications.

The manifestations of the Freeman-Sheldon syndrome (FSS) in four members of a South African family of Xhosa stock have been documented. Orofacial manifestations are a major syndromic component and warrant early, specialized orthodontic intervention. Our protocol for dental management is outlined and suggestions for holistic oro-dental care are provided.

Hypothalamic hamartoma, cerebellar hypoplasia, facial dysmorphism and very atypical combination of polydactyly: is it a new variant of oro-facio-digital syndrome?

We describe a newborn with multiple congenital anomalies consistent with an oro-facio-digital syndrome (OFDS). These are a group of inherited syndromes that have in common anomalies of the tongue (bifid or lobulated tongue with hamartomas), the face (median cleft lip) and the digits (brachydactyly, polydactyly, clinodactyly and/or syndactyly). OFDS has been classified into 11 types. The case described in this paper had manifestations overlapping with OFDS II (Mohr) and OFDS IV (Mohr-Majewski) and OFDS VI (Varadi). We propose that the present patient has a new variation of the OFDS due to the co-existence of the very atypical combination of polydactyly, cerebellar hypoplasia, hypothalamic hamartoma and classical facial findings of OFDS.

Hand involvement in Schmid metaphyseal chondrodysplasia.

Schmid metaphyseal chondrodysplasia (Schmid MCD, MIM 156500) is caused by mutations in the COL10A1 gene and is clinically characterized by short stature, bowed legs, and a waddling gait. Radiographic findings include anterior cupping, sclerosis and splaying of the ribs, diffuse metaphyseal flaring, and irregularity that is most pronounced at the knees, coxa vara, and femoral bowing. We reviewed the radiographs of Schmid MCD patients at the International Skeletal Dysplasia Registry in Los Angeles for evidence of hand involvement. We found hand involvement in 47% (7/15) of cases included in our analysis. These changes were subtle and consisted of shortening of the tubular bones and metaphyseal cupping of the proximal phalanges and metacarpals. Mild hand involvement is a common feature of Schmid MCD.

La mano reumatológica: exploración y tratamiento. Revisión / The rheumatoid hand: assessment and treatment. Review

Puesto que la mano reumatológica es motivo de atención fisioterapéutica diaria, se revisarán en este artículo aquellos aspectos que puedan ser de utilidad para su valoración y posterior tratamiento. Metodología: Revisión bibliográfica en distintas bases de datos (Cochrane, PEDro, Medline y OT seeker), libros y revistas de interés. Resultados: En cuanto a la valoración no existen escalas específicas validadas en España. Las herramientas utilizadas habitualmente por el fisioterapeuta (fuerza, grado de edema, dolor, amplitud articular, destreza para las actividades de la vida diaria) son aconsejadas por algunos autores como medida de la evolución del paciente. Se discuten otros índices de valoración funcional más específicos. En cuanto al tratamiento, las revisiones sistemáticas de los métodos propuestos por la literatura clásica no son nada concluyentes. A pesar de estas limitaciones metodológicas de los trabajos analizados se concluye que los métodos que cuentan con mayor evidencia científica para su aplicación en la mano reumatológica son el láser, la electroestimulación, la electroacupuntura y los ultrasonidos. Conclusiones: Faltan estudios que den soporte a la actividad del fisioterapeuta tanto referente a las escalas de valoración como a las modalidades de tratamiento (AU)

Chronic angle closure glaucoma secondary to frail zonular fibres and spherophakia.

PURPOSE: We describe a 39-year-old Japanese woman with chronic angle closure glaucoma secondary to spherophakia and frail zonular fibres. The patient was 143 cm in height with short fingers and had no family history of eye problems. High intraocular pressure, total optic disc cupping and severe visual field constriction were found in the right eye. METHODS: The patient was treated successfully with trabeculectomy in the right eye and laser iridotomy in the left eye. CONCLUSION: The clinical findings imply that this was a borderline case of Weil-Marchesani syndrome.