Spastic Quadriplegia Research Articles

Derotational Subtrochanteric Osteotomy and External Fixation for the Treatment of Neurogenic Hip Dislocation in Children with Cerebral Palsy: Could This Be a Viable Method of Treatment?

PurposeThe treatment of painful and chronic dislocated hip in children with severe cerebral palsy (CP) is particularly demanding and controversial. Numerous surgical techniques have been described, and their outcomes vary a lot. The purpose of the present study is to evaluate a new method, which combines varus derotational subtrochanteric osteotomy (VDSO) and external osteosynthesis: (VDSOEO).MethodsSix non-ambulatory children with spastic quadriplegia and chronic dislocated painful hips were treated. The technique involved a small incision on the subtrochanteric site of the osteotomy, followed by retention with a single-sided external osteosynthesis with rotational correction capability [swiveling clamp (SC)] for the reduction of the femur head in the acetabulum, and finally by the osteotomy. Hardware was removed without a second intervention four-six months postoperatively and after the osteotomy was healed. Evaluation of the method was based on clinical, functional, and radiological criteria.Results Four patients achieved improved radiological scores. Two patients demonstrated resubluxation during the period of the osteotomy's healing process. However, no patients experienced pain, and all were able to sit post-surgery, while caregivers reported improved capacity for nursing care.ConclusionsIt is our strong belief that this approach can improve the quality of life in children with severe CP and painful and chronic dislocated hips. It is a viable and definitely less invasive procedure than classic pelvic or femur osteotomies.

Novel variants in AP4B1 cause spastic tetraplegia, moderate psychomotor development delay and febrile seizures in a Chinese patient: a case report

IntroductionThe AP4B1 gene encodes a subunit of adaptor protein complex-4 (AP4), a component of intracellular transportation of proteins which plays important roles in neurons. Bi-allelic mutations in AP4B1 cause autosomal recessive spastic paraplegia-47(SPG47).Case presentationHere we present a Chinese patient with spastic tetraplegia, moderate psychomotor development delay and febrile seizures plus. Brain MRIs showed dilated supratentorial ventricle, thin posterior and splenium part of corpus callosum. The patient had little progress through medical treatments and rehabilitating regimens. Whole exome sequencing identified novel compound heterozygous truncating variants c.1207C > T (p.Gln403*) and c.52_53delAC (p.Cys18Glnfs*7) in AP4B1 gene. Causal mutations in AP4B1 have been reported in 29 individuals from 22 families so far, most of which are homozygous mutations.ConclusionsOur study enriched the genetic and phenotypic spectrum of SPG47. Early discovery, diagnosis and proper treatment on the conditions generally increase chances of improvement on the quality of life for patients.

Martsolf syndrome with novel mutation in the TBC1D20 gene in a family from Iran

Warburg Micro syndrome and Martsolf syndrome are phenotypically overlapping autosomal recessive conditions characterized by multiple organ abnormalities involving the ocular, nervous, and endocrine systems. Warburg Micro syndrome, the more severe of the two conditions, is caused by loss of function mutations in RAB3GAP1, RAB3GAP2, RAB18, and TBC1D20 genes, whereas Martsolf syndrome has been attributed to less damaging mutations in RAB3GAP1 and RAB3GAP2 genes. We report the clinical description and molecular characterization of a consanguineous Iranian family with two siblings, a male and a female, with dysmorphic features, bilateral congenital cataracts, optic nerve atrophy, congenital glaucoma, mild to moderate intellectual disability, seizures, hypogonadism, and mild osteoporosis. Spastic quadriplegia with contractures was observed in the male patient, while the female patient showed only mild hyperreflexia. Magnetic resonance imaging scans performed in the male patient showed a normal brain structure. Both siblings had neither microcephaly nor postnatal growth retardation. Whole exome sequencing identified a novel homozygous nonsense mutation [c.1060C>T; p.(Arg354Ter)] in the TBC1D20 gene in both siblings and confirmed the heterozygous carrier status of both parents. This report describes a novel mutation in the TBC1D20 gene in two Iranian patients with Martsolf syndrome, further extending the allelic heterogeneity and phenotypic spectrum of this rare condition. The genotype and phenotype of the patients are compared with those of Martsolf syndrome and Warburg Micro syndrome patients reported in the literature.

Evaluation of the Various Clinical Presentations of Adult CNS Tuberculosis

Background: Central nervous system (CNS) involvement is one of the most important extrapulmonary manifestations of tuberculosis (TB) causing considerable mortality and morbidity. Presentations of CNS TB are extremely variable. Treatments are generally more effective if the disease can be detected early. This study is to find out the various clinical patterns and investigation findings that might help in early detection of CNS TB.
 Objective: This study was conducted to detect various clinical manifestations of adult CNS TB at an earlier stage of evaluation.
 Methods: This was a hospital based observational study (cross sectional type) conducted on 30 patients of CNS TB who were admitted in Sir Salimullah Medical College Mitford Hospital, Dhaka during a period of 6 months from October 2013 to April 2014
 Results: Among the participants 53% were male and 47% were female, with a male female ratio of 1.13: 1. Mean age of the participants was 35.17±6.14 years. Tuberculosis involving brain (i.e. cranial TB) was most common (30.4%) in 15-24 years age group whereas spinal form of TB was most common (42.8%) in 25-34 years age group. Mean age of the participants having Brain TB was 36.46±6.90 years. Mean age of the participants having spinal TB was 32.36±12.52 years. Highest number of the cranial forms of TB was tuberculoma (52.2%) in this study and was found mostly in the young adults. Spinal TB was found in 25-34 years age group in highest number, all but one were Potts disease. Tuberculoma and tuberculous meningitis had an equal distribution in female sex while males had a higher (53.8%) occurrence of tuberculoma. On the other hand, spinal involvement was commoner in male sex (43.5%).Fever was the most common symptom noted in all forms of CNS TB patients (78.26% for brain and 71.43% for spinal cord TB patients) followed by headache and loss of consciousness representing 2nd and 3rd common symptom in brain TB patients. Most common clinical signs in brain TB were signs of meningeal irritation (65.22%), cranial nerve palsies and papillodema while spastic paraparesis with sensory level being the commonest in spinal cases. Tuberculoma was the most frequent neuro-radiologic findinds in case of brain TB patients and paraspinal soft tissue shadow with vertebral collapse was commoner in spinal TB patients.
 Conclusion: This study has highlighted the relative frequency of various types of brain and spinal TB lesions along with the symptoms, signs and laboratory findings in Bangladeshi adult patients. In Bangladesh, tuberculosis should be always an important differential diagnosis in patients of fever with headache as well as spastic paraplegia or quadriplegia for any duration in any sex group.
 J Dhaka Medical College, Vol. 28, No.1, April, 2019, Page 76-84

Cerebral palsy in children: a clinical overview.

Cerebral palsy (CP) is a disorder characterized by abnormal tone, posture and movement and clinically classified based on the predominant motor syndrome—spastic hemiplegia, spastic diplegia, spastic quadriplegia, and extrapyramidal or dyskinetic. The incidence of CP is 2–3 per 1,000 live births. Prematurity and low birthweight are important risk factors for CP; however, multiple other factors have been associated with an increased risk for CP, including maternal infections, and multiple gestation. In most cases of CP the initial injury to the brain occurs during early fetal brain development; intracerebral hemorrhage and periventricular leukomalacia are the main pathologic findings found in preterm infants who develop CP. The diagnosis of CP is primarily based on clinical findings. Early diagnosis is possible based on a combination of clinical history, use of standardized neuromotor assessment and findings on magnetic resonance imaging (MRI); however, in most clinical settings CP is more reliably recognized by 2 years of age. MRI scan is indicated to delineate the extent of brain lesions and to identify congenital brain malformations. Genetic tests and tests for inborn errors of metabolism are indicated based on clinical findings to identify specific disorders. Because CP is associated with multiple associated and secondary medical conditions, its management requires a multidisciplinary team approach. Most children with CP grow up to be productive adults.

Decreased mitochondrial DNA copy number in children with cerebral palsy quantified by droplet digital PCR

BackgroundMitochondrial DNA copy number is a potential biomarker for mitochondrial dysfunction and is involved in a variety of disease states including autism, neurodegenerative diseases and traumatic brain injury, but few studies on mitochondrial DNA copy number in cerebral palsy have been reported. Therefore, this study aims to investigate the role of mitochondrial DNA copy number in children with cerebral palsy. MethodsA total of 104 children with cerebral palsy and 78 typically developing children were enrolled in this study. All children with cerebral palsy were diagnosed according to clinical criteria and furtherly divided into clinical subtypes. Mitochondrial DNA copy number was quantified by droplet digital PCR. ResultsWe observed a significant reduction in mitochondrial DNA copy number from children with cerebral palsy comparing to healthy controls (216.76 ± 71.39 vs 359.66 ± 72.78, p < 0.001). An upward trend in mitochondrial DNA copy number alteration with the increase of age was found in healthy controls rather than in children with cerebral palsy. In addition, the mitochondrial DNA copy number in children with spastic hemiplegia was higher than that in children with spastic quadriplegia (152.27 ± 49.78 vs 90.64 ± 21.55, p = 0.001). ConclusionsOur results suggest that on the basis of accurate quantification by droplet digital PCR, the declined mitochondrial DNA copy number probably has certain implications for mitochondrial dysfunction in children with cerebral palsy, which provides a new clue for the investigation on the molecular mechanism and clinical characteristics of cerebral palsy.

A de novo heterozygous mutation in KCNC2 gene implicated in severe developmental and epileptic encephalopathy

An increasing number of developmental and epileptic encephalopathies have been correlated with variants of ion channel genes, and in particular of potassium channels genes, such as KCNA1, KCNA2, KCNB1, KCNQ2, KCTD7 and KCNT1. Here we report a child with an early severe developmental and epileptic encephalopathy, spastic tetraplegia, opisthotonos attacks. The whole exome sequencing showed the de novo heterozygous variant c.1411G>C (p.Val471Leu) in the KCNC2 gene. Although this is, to our knowledge, the first case of encephalopathy associated with a KCNC2 gene variant, and further confirmatory studies are needed, previous preclinical and clinical evidence seems to suggest that KCNC2 is a new candidate epilepsy gene.

Mutations of MACF1, Encoding Microtubule-Actin Crosslinking-Factor 1, Cause Spectraplakinopathy

As a member of spectraplakin family of cytoskeletal crosslinking proteins, microtubule-actin crosslinking factor 1 (MACF1) controls cytoskeleton network dynamics. Knockout of Macf1 in mice resulted in the developmental retardation and embryonic lethality. Spectraplakinopathy type I, a novel neuromuscular condition characterized by periodic hypotonia, lax muscles, joint contracture, and diminished motor skill, was reported to be associated with heterozygous genomic duplication involving the MACF1 loci, with incomplete penetrance and highly variable clinical presentation in a single pedigree. In this study, parental-derived compound heterozygous novel missense mutations of MACF1, c.1517C>T (p.Thr506Ile) and c.11654T>C (p.Ile3885Thr), were found to co-segregate with disease status in two affected brothers presenting with progressive spastic tetraplegia, dystonia, joint contracture, feeding difficulty and developmental delay. We speculated that MACF1 mutations cause spectraplakinopathy inherited in an autosomal recessive manner. Our clinical findings expanded the phenotype of this neuromuscular disorder and provided new insights into the function of MACF1.

Magnetic resonance imaging findings in patients with cerebral palsy in Duhok, Iraq: Case series

Aim: Magnetic resonance imaging is an important technique for evaluating structural abnormalities in the brain. Many neurologists and pediatricians refer cerebral palsy patients to conventional magnetic resonance imaging. The objective of this study was to assess magnetic resonance imaging findings in children with cerebral palsy and to research whether it can predict the etiology or pathogenesis of this disease.Methods: This case study was carried out at Azadi General Hospital from the 1st of July 2016 until the 28th of February 2017. A total of 48 patients who were diagnosed with cerebral palsy were included in the study. They all underwent cranial magnetic resonance imaging under general anaesthesia, and results were compared statistically. Results: The male to female ratio was 2.4:1. Magnetic resonance imaging was abnormal in 87.5%. Diffuse encephalopathy was seen in 56.2% of cases, periventricular leukomalacia was detected in 18.8%, changes of ischemic lesion were seen in 4.2 %, congenital malformations in 8.3% and normal scan was seen in 12.5% of cases. Among the clinical sub-types of cerebral palsy, spastic diplegia was the most common (47.9%), followed by spastic quadriplegia (35.4%), spastic hemiplegia (10.4%), and choreoathetoid cerebral palsy (6.3%). Conclusions: This study concluded that brain changes in magnetic resonance imaging can detect the pathogenesis of cerebral palsy and is diagnostic in congenital brain malformations.

Risk factors of global developmental delay in infants and children with cerebral palsy in Mid-Delta Region, lower Egypt

Background Cerebral palsy (CP) is a physical disability that affects movement and posture; it is a term that refers to a group of disorders affecting a person’s ability to move, due to damage to the developing brain either during pregnancy or shortly after birth. CP can affect body movement, muscle control, muscle coordination, muscle tone, reflex, posture, and balance. Aim The aim of the study was to identify the most important risk factors that are implicated in the etiology of global developmental delay in children with CP. Patients and methods This cross-sectional study was carried out on 100 patients with the diagnosis of CP aged less than 17 years who were attending the Pediatric Neurology Outpatient Clinic of Tanta University Hospital during the period from August 2019 to June 2020. Results The most common risk factors associated with severe mental retardation were low socioeconomic level, epilepsy, especially if uncontrolled, antiepileptic drugs, especially Na valproate alone or in combination with levetiracetam or topiramate, perinatal hypoxia, postencephalitic etiology, congenital brain anomalies, spastic quadriplegia, and mixed type. The most common risk factors associated with severe developmental delay were perinatal hypoxia, congenital infection, and congenital brain anomalies. Conclusion The most common risk factors of CP in this study were perinatal hypoxia, prematurity, and prenatal hypoxia.

Atlantoaxoid subluxation by suboccipital Pott's disease: Arthrodesis using the Harms technique. About a case and review of the literature

Introduction: The suboccipital location of Pott′s disease is exceptional, and may be complicated by compression of the bulbomedullary junction. Case Report: We report the case of a young patient of 32 years of age, received in a table of spastic tetraplegia preceded by cervicalgia without associated sensory or sphincter disorders. Computed tomography and magnetic resonance imaging of the cervico-occipital hinge showed C1-C2 subluxation with osteolysis of the C1 arches, bone sequestration, and anterior compression of the bulbomedullary junction, requiring arthrodesis using the Harms technique. Diagnostic confirmation was obtained by pathological examination of bone fragments and epidural tissue removed per operation. Tuberculosis chemotherapy was started for 16 months. Progression was favorable with motor recovery allowing unaided walking. Conclusion: The surgical indication of these all tuberculosis localizations depends on the presence of bulbomedullary compression and/or cervico-occipital hinge instability.

Rehabilitation of spastic tetraplegia in pediatrics: advantages of hydro-kinesitherapy

Background: At the base of this study there is the rehabilitation of spastic tetraplegia observed in a pediatric setting. Spastic tetralgia is a severe form of cerebral palsy (PCI), including all four limbs and characterized by rigidity or permanent contraction of the affected muscles. The latter is a persistent but not immutable disorder of posture and movement due to alterations in brain function due to pre-, peri- or post-natal causes, before the growth and development of the central nervous system is completed. Objective: To demonstrate how a treatment of at least 6 months can give satisfactory results, even in pathological conditions such as tetraplegia. Attention is paid to treatment methods, and therefore to the rehabilitation of this pathology from the point of view of physio-kinesitherapy. Methodology: An investigation and an experimental study was conducted using interviews and treatments of referred patients 2-10 years old. The interviews were carried out with parents coming from Tirana and suburbs. Data collected showed us the specific needs of each child living with the family and it was created a tailored rehabilitation plan for each of them. Results: Despite suffering from a severe condition, there have been significant improvements in the generic framework, especially on the activities of daily life, thus alleviating the difficulties these children are facing. The handling of each child with empathy and personalized care is needed to obtain satisfactory results. Conclusion: Results showed how all the children taken in charge had an improvement in their quality of life. Their communication and even collaborative skills have improved.

PREVALENCE AND RISK FACTORS ASSOCIATED WITH CONSTIPATION CEREBRAL PALSY CHILDREN IN PAKISTAN

Objective: To find prevalence of constipation and associated risk factors among cerebral palsy. Material &amp; Methods: The Cross sectional and case control study was conducted in physiotherapy department of National Institute of Rehabilitation Medicine Islamabad (NIRM) after approval from director of NIRM. The inclusion criteria were CP children with age between 2-12 years and Children with any other systemic co morbidities, physical deformity in GIT, intellectual disability and recent traumatic brain injury were excluded. A total of n=170 subjects fulfilled the inclusion criteria and were part of the study. The data was collected in term of age, gender, body mass index (BMI), types of CP children, fluid, fiber and calories intake. Spasticity and functional independence were also measured through Modified Ashworth scale (MAS) and Gross Motor Function Classification System (GMFCS) respectively. The constipation in CP children was measure through defecation frequency. Defecation frequency measured less than three times a week was considered constipation and Constipation assessment scale (CAS). The data was described in the form of frequency, percentage, mean, standard deviation, correlation, chi-square and p-value. Results: The results showed that all characteristics including age, spasticity, functional independence, fluid intake, calories intake, fiber intake, physiological and topographical type of CP children showed significant association (p&lt;0.05) with defecation frequency and constipation severity except BMI and gender (p≥0.05). Conclusion: Constipation is highly prevalent in cerebral palsy. The early age, increased spasticity, decreased functional independence related to increased constipation CP children. It was also concluded that low fluid, calories and fiber intake were also contributing factor in development of constipation. The children with spastic cerebral palsy and quadriplegia are more related to constipation than other kind of cerebral palsy. Keywords: Cerebral palsy, constipation, constipation severity scale, defecation frequency, modified ashworth scale, gross motor functional classification scale.

3244 Acute Massive Gastric Distention in an Adult Patient With Cerebral Palsy

INTRODUCTION: Cerebral Palsy (CP) is a motor impairment secondary to neurological abnormalities in the central and peripheral nervous systems. CP can affect the functioning of the gastrointestinal system. Common complications include dysphagia, constipation, regurgitation, vomiting and gastroesophageal reflux. Severe gastric distension is a very rare complication of CP with a high mortality risk. We present a case of severe gastric distension in a patient with CP. CASE DESCRIPTION/METHODS: A non-verbal 39-year-old man with history of CP, spastic quadriplegia, deep vein thrombosis, and obstipation status post colectomy and subtotal ileostomy presented with a 2-day history of poor oral intake, abdominal distention, and decreased ileostomy output. Patient had a similar presentation one-month prior. Vitals were within normal. Physical exam showed abdominal distension, abdominal tenderness, absent bowel sounds and tympany to percussion. Labs were normal except for hemoglobin of 8.3 g/dL, blood urea nitrogen of 42 mg/dL and a creatinine of 1.65 mg/dL. Computerized tomography showed markedly dilated stomach with air-fluid levels. Patient was placed on nothing by mouth. A nasogastric tube was placed to suction. An endoscopy was done that was negative for gastric outlet obstruction (GOO). Xrays showed resolution of the gastric distension. Patient tolerated liquids and then solids. He began to have stool output from the ileostomy and was discharged. DISCUSSION: Gastric distension in patients with CP is not fully understood. Gastric emptying and motility of the foregut are regulated by the vagus nerve. Predisposing factors include autonomic neuropathy, neuromuscular incoordination, air swallowing and malposition of the stomach. Death may be due to respiratory compromise by lung compression from a dilated stomach, or rupture of the stomach. Gastric distension can be seen in patients with GOO or diabetes mellitus with gastroparesis. Another cause is severe kyphoscoliosis of the vertebral columns causing malpositioning and posterior displacement resulting in mechanical obstruction preventing spontaneous decompression. In cases of recurrent or severe gastric distension, worsening of symptoms, or non-resolving distension after supportive management a venting gastrostomy may be needed. Severe gastric dilatation, with or without rupture, should be considered a potential cause of unexpected death in individuals with severe mental and physical disabilities.

Epilepsy in children with cerebral palsy

Cerebral palsy is the most common cause of severe neuromotor disorders in children. Cerebral palsy are often associated with disorder of cognition, communication, and behavior ([1]Bax M. Goldstein M. Rosenbaum P. et al.Proposed definition and classification of cerebral palsy.Dev Med Child Neurol. 2005; 47: 571-576Google Scholar), as well as epilepsy. Epileptic seizures are most common in children with spastic quadriplegia and hemiplegia ([2]Ashwal S. Russman B.S. Blasco P.A. et al.Practiceparameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child NeurologySociety.Neuro. 1996; 97: 192-197Google Scholar). In spastic diplegia, the incidence is lower, while the frequency of epilepsy in both the diskinetic and the ataxic form is extremely low ([3]Arts W.F. Geerts A.T. When to start drug treatment for childhood epilepsy: the clinical-epidemiological evidence.Eur J Paediatr Neurol. 2009; 13: 93-101Google Scholar). Early drug administration (after the first attack) is advised for the risk of relapse, epi status and possible pharmacoresistence ([4]Delgado M.R. Riela A.R. Discontinuation of antiepileptic drug treatment after teo seizure-free zears in children with cerebral palsy.Pedaitrics. 1996; 97: 192-197Google Scholar). We followed the 51 patients. The dominant form of CP was spastic quadriparesis and spastic hemiparesis. The dominant type of attack is generalized attacks, then partial with and without secondary generalization as well as infantile spasms. The majority of patients used polytherapy followed by mono- and dual therapy. Remission is achieved in more than half of patients. All patients who exhibited pharmacoresistence were in the field of polytherapy.

A Study on Efficacy of Respiratory Exercises Coupled with Neurodevelopmental Treatment on Pulmonary Function of Children with Spastic Quadriplegic Cerebral Palsy

Cerebral palsy is a group of condition characterized by motor dysfunction due to non-progressive brain damage early in life. They may also have decreased mobility, restriction in physical activity and limitation in functional capacities, Along with motor dysfunction, children with cerebral palsy can have abnormality of respiratory function This study was intended to study the efficacy of Respiratory exercises along with Neurodevelopmental treatment in Pulmonary function of children with Spastic quadriplegic cerebral palsy.

Osseous Metaplasia: An Unusual and Poorly Understood Finding in Gastric Polyps

Abstract Osseous metaplasia (OM) is an uncommon finding in gastrointestinal tract biopsies. Metaplastic bone formation has been predominantly reported in the lower GI tract in a background of benign and malignant neoplasms, as well as nonneoplastic inflammatory conditions. OM in the stomach is extremely rare, with less than 10 cases reported in the English literature to date. We present two cases of gastric OM encountered at one institution among more than 10,000 stomach polyps examined since 1994. The first is a 46-year-old female with spastic quadriplegia, peptic ulcer disease, and a jejunal feeding tube who had multiple gastric hyperplastic polyps removed over a 13-year period. The most recent polypectomy revealed a 3-cm gastric adenoma with benign bone formation in the stroma. The second case is of a 67-year-old asymptomatic male with a remote history of intestinal metaplasia and atrophy of the stomach who underwent upper endoscopy and removal of a 1-cm polyp. Sections consisted of hyperplastic foveolar epithelium with focal ossification. Both polyps showed acute and chronic inflammation and stromal fibrosis, and they lacked Helicobacter infection. Mechanisms driving gastrointestinal OM have been proposed since the first reported cases in the early 1900s. The most widely accepted theory is that osteogenic factors released by the neoplastic or inflammatory tissue induce undifferentiated stromal mesenchymal cells or fibroblasts to undergo transformation to osteoblasts. However, with gastrointestinal biopsies being one of the most common specimens, the picture remains incomplete as only very rare cases show bone formation, warranting further research. Although gastrointestinal OM appears to be clinically insignificant, long-term studies have yet to be performed. Nevertheless, it is crucial for pathologists to be aware of this phenomenon in order to avoid misdiagnosing OM as a primary mesenchymal neoplasm or bone invasion in cases of OM arising in the background of malignancy.

Whether the newly modified rhizotomy protocol is applicable to guide single-level approach SDR to treat spastic quadriplegia and diplegia in pediatric patients with cerebral palsy?

PurposeOur aim was to test whether the newly modified rhizotomy protocol which could be effectively used to guide single-level approach selective dorsal rhizotomy (SL-SDR) to treat spastic hemiplegic cases by mainly releasing those spastic muscles (target muscles) marked pre-operatively in their lower limbs was still applicable in spastic quadriplegic or diplegic cerebral palsy (CP) cases in pediatric population.MethodsIn the current study, we retrospectively conducted a cohort review of cases younger than 14 years of age diagnosed with spastic quadriplegic or diplegic CP who undergone our modified protocol-guided SL-SDR in the Department of Neurosurgery, Children’s Hospital of Shanghai since July 2016 to November 2017 with at least 12 months post-op intensive rehabilitation program (pre-op GMFCS level-based). Clinical data including demographics, intra-operative EMG responses interpretation, and relevant assessment of included cases were taken from the database. Inclusion and exclusion criteria were set for the selection of patients in the current study. Muscle tone (modified Ashworth scale) and strength of those spastic muscles (muscle strength grading scale), range of motion (ROM) of those joints involved, the level of Gross Motor Function Classification System (GMFCS), and Gross Motor Function Measure 66 items (GMFM-66) score of those cases were our focus.ResultsA total of 86 eligible cases were included in our study (62 boys). Among these patients, 61.6% were quadriplegic. Pre-operatively, almost 2/3 of our cases were with GMFCS levels II and III. Mean age at the time of surgery in these cases was 6.2 (3.5–12) years. Pre-op assessment marked 582 target muscles in these patients. Numbers of nerve rootlets tested during SDR procedure were between 52 and 84 across our cases, with a mean of 66.5 ± 6.7/case. Among those tested (5721 in 86 cases), 47.9% (2740) were identified as lower limb-related sensory rootlets. Our protocol successfully differentiated sensory rootlets which were considered to be associated with spasticity of target muscles across all our 86 cases (ranged from 3 to 21). Based on our protocol, 871 dorsal nerve rootlets were sectioned 50%, and 78 were cut 75%. Muscle tone of those target muscles reduced significantly right after SL-SDR procedure (3 weeks post- vs. pre-op, 1.7 ± 0.5 vs. 2.6 ± 0.7). After an intensive rehabilitation program for 19.9 ± 6.0 months, muscle tone continued to decrease to 1.4 ± 0.5. With the reduction of muscle tone, strength of those target muscles in our cases improved dramatically with statistical significance achieved (3.9 ± 1.0 at the time of last follow-up vs. 3.3 ± 0.8 pre-op), and as well as ROM. Increase in GMFCS level and GMFM-66 score was observed at the time of last follow-up with a mean of 0.4 ± 0.6 and 6.1 ± 3.2, respectively, when compared with that at pre-op. In 81 cases with their pre-op GMFCS levels II to V, 27 (33.3%) presented improvement with regard to GMFCS level upgrade, among which 4 (4.9%) even upgraded over 2 levels. Better results with regard to upgrading in level of GMFCS were observed in cases with pre-op levels II and III when compared with those with levels IV and V (24/57 vs. 3/24). Upgrading percentage in cases younger than 6 years at surgery was significantly greater than in those older (23/56 vs. 4/25). Cases with their pre-op GMFM-66 score ≥ 50 had greater score increase of GMFM-66 when compared with those less (7.1 ± 3.4 vs. 5.1 ± 2.8). In the meanwhile, better score improvement was revealed in cases when SDR performed at younger age (6.9 ± 3.3 in case ≤ 6 years vs. 4.7 ± 2.7 in case > 6 years). No permanent surgery-related complications were recorded in the current study.ConclusionSL-SDR when guided by our newly modified rhizotomy protocol was still feasible to treat pediatric CP cases with spastic quadriplegia and diplegia. Cases in this condition could benefit from such a procedure when followed by our intensive rehabilitation program with regard to their motor function.

DEGS1 variant causes neurological disorder.

Sphingolipidoses are monogenic lipid storage diseases caused by variants in enzymes of lipid synthesis and metabolism. We describe an autosomal recessive complex neurological disorder affecting consanguineous kindred. All four affected individuals, born at term following normal pregnancies, had mild to severe intellectual disability, spastic quadriplegia, scoliosis and epilepsy in most, with no dysmorphic features. Brain MRI findings were suggestive of leukodystrophy, with abnormal hyperintense signal in the periventricular perioccipital region and thinning of the body of corpus callosum. Notably, all affected individuals were asymptomatic at early infancy and developed normally until the age of 8-18 months, when deterioration ensued. Homozygosity mapping identified a single 8.7 Mb disease-associated locus on chromosome 1q41-1q42.13 between rs1511695 and rs537250 (two-point LOD score 2.1). Whole exome sequencing, validated through Sanger sequencing, identified within this locus a single disease-associated homozygous variant in DEGS1, encoding C4-dihydroceramide desaturase, an enzyme of the ceramide synthesis pathway. The missense variant, segregating within the family as expected for recessive heredity, affects an evolutionary-conserved amino acid of all isoforms of DEGS1 (c.656A>G, c.764A>G; p.(N219S), p.(N255S)) and was not found in a homozygous state in ExAC and gnomAD databases or in 300 ethnically matched individuals. Lipidomcs analysis of whole blood of affected individuals demonstrated augmented levels of dihydroceramides, dihydrosphingosine, dihydrosphingosine-1-phosphate and dihydrosphingomyelins with reduced levels of ceramide, sphingosine, sphingosine-1-phosphate and monohexosylceramides, as expected in malfunction of C4-dihydroceramide desaturase. Thus, we describe a sphingolipidosis causing a severe regressive neurological disease.

Use of outcome measures in children with severe cerebral palsy: A survey of U.K. physiotherapists.

To investigate the use of outcome measures for children with cerebral palsy (CP) by paediatric physiotherapists (PTs) who are based in the United Kingdom, as limited research exists regarding their use in this population, and to explore therapists' use of measures within different Gross Motor Function Classification System (GMFCS) levels and for different types of CP. A six-item online survey was advertised through two paediatric therapy special interest groups inviting physiotherapists to participate. Descriptive statistics (range, frequencies, and percentages) were used to analyse survey data. Two hundred and seven physiotherapists returned completed survey questionnaires. One hundred and seventy-six (85%) therapists reported using a wide variety of outcome measures (57). Eighty-one per cent of therapists' responses for having "most difficulty" in identifying responsive outcome measures were for children with impaired mobility at GMFCS Levels IV-V and children with more significant body involvement (76%), for example, spastic quadriplegia or dyskinesia. Eighty-six per cent of therapists' responses for having "greatest ease" of identifying responsive outcome measures were for children within GMFCS Levels I-III and for children with less significant body involvement (72%), for example, hemiplegia. The variety of outcome measures used by therapists with children within GMFCS IV-V was less (16). The majority (85%) of the PTs surveyed used outcome measures with children with CP, but 81% perceived a difficulty in identifying responsive measures for children with more severe impairments who are classified as GMFCS IV-V. The reasons for this perceived difficulty warrant investigation and may suggest a need for training regarding relevant measures and/or a need to develop new measures for this group of children.