[ ISSN : 2573-3680 ]
Rubinstein-Taybi Syndrome; Cervical Spinal Stenosis; Spasticity; Myelopathy
Rubinstein-Taybi Syndrome (RTS) is a rare autosomal dominant genetic disease characterized by growth deficiency, broad thumbs and great toes, intellectual disability and characteristic craniofacial appearance. Neurological manifestations of RTS include: seizures, primary brain tumors, cranio-spinal and posterior fossa anomalies. We describe a 21 year-old male with past medical history of congenital heart disease, kypho-scoliosis, intellectual disability, and global developmental delay. Neurological examination revealed spasticity with atrophic changes in all the extremities. Brain MRI was unremarkable and spinal MRI revealed multi-level degenerative changes in cervical spine with cervical spinal stenosis for which patient underwent C4-C6 laminectomy with postero-lateral fusion. In spite of de-compressive surgery, the spasticity persisted making RTS as the most likely etiology of spasticity. Patient spasticity was managed with baclofen and tizanidine. The goal of this case report is to extend our current knowledge on RTS and to define new international guidelines for diagnosis, care and treatment.
Rubinstein-Taybi syndrome (RTS) or Broad thumb-hallux syndrome is an extremely rare congenital disorder characterized by short stature, intellectual disability, distinctive facial features, broad thumbs and first toes base, congenital cardiac abnormalities and skeletal anomalies. Although patients frequently present with cardiorespiratory, musculoskeletal, genitourinary and endocrine abnormalities, neurological manifestations are not rare. The most common neurological manifestations of RTS include: seizures, primary brain tumors, cranio-spinal and posterior fossa anomalies [1]. The estimated prevalence of RTS is one case per 125,000 live births [2]. Associations between compressed spinal cord due to fusion of vertebrae and RTS has been reported before and it was suggested that laminectomy and spinal cord untethering procedures can benefit most of the patients [3,4]. Myelopathy is the clinical manifestation of spinal cord compression causing upper motor neuron neurologic dysfunction such as gait disturbance, increased reflexes, spasticity, muscle weakness and/or numbness.
We report a 21 years old male patient who presented to the neuromuscular clinic with spasticity in bilateral upper extremities. He was diagnosed with Rubinstein-Taybi syndrome at the age of 15 based on clinical features. A diagnosis of RTS was later con-firmed on genetic testing.
He had a past surgical history of congenital cervical stenosis with myelopathy for which he underwent C4-C6 laminectomy and posteriolateral fusion, scoliosis, kyphosis, repaired congenital heart defects (ASD, Pulmonary stenosis and PDA), intellectual disability and global developmental delay. Patient’s mother is the informant and she takes care of his Activities of Daily Living (ADLs). Patient is wheelchair bound and communicates by nodding his head for yes or no. His current medications include Baclofen 10 mg BID and Tizanidine 2mg BID, for severe spasticity.
Neurological examination was significant for atrophic changes in bilateral upper and lower extremities. Patient had increased tone with spasticity in bilateral upper extremities, more on the left compared to the right. Right elbow demonstrated full range of motion while left elbow revealed contractures at 145 degrees. Patient had a Brain MRI in 2011, which was unremarkable.
Thoracolumbar MRI in 2013 revealed worsening of thoracic scoliosis compared to the previous study. There was a nonspecific focal hyper-intense T2 signal in the Conus medullaris of cervical spine. Multilevel degenerative changes of cervical spine with post surgical changes from C4 through C6 including cervical cord volume loss and abnormal signal change were noted.
Rubinstein-Taybi Syndrome (RTS) is a rare autosomal dominant genetic disorder. Rubenstein and Taybi first reported this in 1963 on seven cases which included a group of anomalies such as short, broad thumbs and great toes, facial abnormalities, psychomotor retardation, highly arched palates and history of recurrent respiratory infections [5]. It is associated with congenital anomalies of cardiovascular system such as ventricular septal defect, patent ductus arteriosus, coarctation and stenosis of the aorta and pulmonic stenosis [6]. It is characterized by mutations in the CREB-binding protein (CREBBP) gene and it has been suggested that a micro-deletion in chromosome segment 16p13.3 could be the cause [7,8]. Alterations in the E1Abinding protein p300 (EP300) can also cause this disorder [9,10] Cervical vertebral abnormalities as C1-C2 instability, osodontoideum, hypoplasia of the dens and fusion of the cervical vertebrae has been reported, with possible stenosis at the craniovertebral junction, which may cause cervical myelopathy [11]. Tanaka et al suggested that some underlying conditions of RTS may mask the symptoms of a tethered spinal cord and careful attention to the symptoms is necessary to prevent further neurological problems [4]. We describe a patient with known/confirmed diagnosis of RTS who presented with spasticity in bilateral upper extremities. It is hard to predict the exact etiology of spasticity but based on the fact that cervical cord stenosis was fixed with laminectomy and postero-lateral fusion, RTS remains the only possible cause of patient’s symptoms. We report an interesting finding in this patient, which is probably a sequel to this devastating disease. Early recognition and treatment can help improve the quality of life in most of these patients.
RTS is an extremely rare condition for which although some clinical aspects have been clearly identified, a lot of multicenter studies are needed to expand our current knowledge on the clinical phenotype. Cervical vertebrae anomalies are common manifestations of RTS. Although laminectomy and reducing spinal cord compression can lead to improvement in most patients, some patients will still experience myelopathy symptoms and special attention should be paid to prevent further neurological consequences. We report an interesting case of RTS with spasticity in all the extremities. The ultimate goal of this case report is to extend our current knowledge on RTS and to define new international guidelines for diagnosis, care and treatment of patients with RTS. Early intervention, special education, vocational training to address developmental disabilities is critical in the management of this rare disorder.
Moheb N, Khosa S, Trikamji B and Mishra SK. Neurological Manifestations of Rubinstein-Taybi syndrome: A Case Report. SM J Clin Med. 2018; 4(1): 1032s1
The purpose of this statement is none other than to highlight the importance of ethical standards and quality required in basic and applied research currently being done so we can subsequently inform health care professionals of new developments that are taking place in this area.
Ma. Esperanza Rodríguez-van Lier*
Chemotherapy is commonly used in cancer treatment. So far, chemotherapy agents can be categorized into three types: classical chemotherapeutic drugs, molecular target agents and cellular machineries target drugs.
Ziyou Wang1,2 and Zunnan Huang1,2*
Blood transfusion can cause some transfusion adverse reactions. In order to understand the incidence of adverse transfusion reactions, we performed a meta-analysis in Chinese hospitals. Of 809 literatures, seven studies involving a total of 211, 050 patients with blood transfusion treatment were included in this meta-analysis. Meta-analysis showed that the total incidence of adverse reactions was 0.4% [95% CI (0.2, 0.9), P < 0.0001]. Further subgroup analysis showed that the incidence of febrile and allergic reactions was 0.2% [95% CI (0.1, 0.5), P < 0.0001] and 0.2% [95% CI (0.1, 0.3), P < 0.0001], respectively. The common blood components caused adverse reactions were red blood cell, plasama, and platelet in clinical practice.
Yulu Gao1 , Qinyun Li2 , Zongshuai Gao2 , Yunxia Zhu4 , Yanqiu Liao5 , Changtai Zhu2 *# , Yongning Sun3 *#
Background: CT scanning remains one of the most routinely used diagnostic tools in a setting of Interstitial Lung Disease (ILD). New and improved technologies, such as High Resolution Computer Tomography (HRCT) have revolutionized the quality of imaging, leading to a prominent increase in number of incidental findings that may or may not be of any clinical significance. The aim of this study was to evaluate the prevalence of incidental findings on thoracic CT and their clinical significance.
Methods: Retrospective analysis was conducted on a cohort of 84 patients referred to our academic center as cases of ILD. Patients were referred for further evaluation between January 2000 and January 2014 and were followed over the disease course. CT scans were done annually as part of clinical management and patients were screened for any incidental findings. All incidental findings were reviewed, recorded in a clinical database and followed up on subsequent visits.
Results: 25 (30%) patients were found to have incidental findings. Liver abnormalities were found in 12 (14.29 %) patients. 11(13.10 %) patients were reported to have coronary artery calcifications. 5 (5.95 %) and 3 (3.57%) patients had thyroid abnormalities and renal cysts, respectively. A malignant lesion was found in 1 patient each in liver and thyroid abnormality subgroup.
Conclusion: Incidental findings are common on thoracic CT scans providing valuable and unexpected findings which warrant investigation by health care providers to exclude malignant processes.
Sonu Sahni1,2*, Sameer Verma1,2, Reeju S Thomas1 , Barbara Capozzi3 and Arunabh Talwar1,2
Hepatitis C Virus infection (HCV) is an increasing public health concern with an estimated 184 million people infected worldwide and approximately 350.000 yearly deaths from HCV-related complications.
Nesrine Gamal and Pietro Andreone*
We report a case of large cell undifferentiated lung carcinoma in a middle aged patient with previously treated tuberculosis and scarring. 20 pack years of smoking history was noted. He presented with metastasis at multiple sites including trochanter, liver and acute bilateral lateral rectus palsy. Chest radiography showed fibrosis of right upper zone with homogenous opacity. Sputum examination for AFB was negative. Computerized tomography of the thorax showed an irregular heterogeneously enhancing mass involving right upper lobe with cavitation, necrosis along with lymph node involvement and the erosion of the 4th rib with liver metastasis. Radiography of hip joint was suggestive of lesser trochanteric metastasis. MRI brain was suggestive of mass at base of brain in parasellar area. Fine needle aspiration cytology and CT guided biopsy confirmed undifferentiated large cell carcinoma of lung. Tuberculosis and smoking may increase the risk of lung scarring and malignancy and pulmonary scarring may be associated with increased lung carcinoma in ipsilateral lung. Clinician needs to be more sensitive to look for malignancy association particularly in patient with or previously treated for tuberculosis and even more emphasis to be laid if scarring of lung is observed.
Sreenivasa Rao Sudulagunta1 *, Shyamala Krishnaswamy Kothandapani2 , Mahesh Babu Sodalagunta3 , Hadi Khorram2 , Mona Sepehrar4 and Zahra Noroozpour1
Systemic Sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs, pronounced alterations in the microvasculature and frequent cellular and humoral immunity abnormalities. The rheumatic involvement of SSc is polymorphic and can reveal the disease or may appear during the course of its progression. Musculoskeletal involvement is dominated by non specific arthralgia, polyarthritis, and bony resorption especially acro-osteolysis. The diagnosis of these rheumatic manifestations is generally based on x rays examination. Musculoskeletal involvement in SSc is generally relieved with Non Steroidal Anti-Inflammatory Drugs (NSAID) or low dose of corticotherapy. The immunosuppressive therapy is used in corticoid-resistant or corticoid-dependent forms such us méthotrexate. The aim of our review is to presents an overview of the different osteoarticular and muscular involvement in SSc, their diagnosis and management.
Nessrine Akasbi*, Fatima Ezzahra Abourazzak and Taoufik Harzy
Sedigheh Mirhashemi1 , Mohammad Hosein Kalantar Motamedi1 *, Amir Hossein Mirhashemi2 and Hamid Reza Rasouli1
We encountered two autopsy cases of huge cardiomegaly with over 1000g in weight. Histochemical characteristics were examined using conventional staining including HE and Azan stains and immunohistochemical staining using antibodies against Complement Component 9 (CC9), RNA Binding Protein Motif 3(RBM3), Endothelial Type NO Synthase (eNOS) and Hypoxic Inducible Factor1α (HIF1). The reactive area with anti CC9 antibody, which presumed to be a marker of hypoxic change of myocardium, overlapped with eosinophilic area by HE and basophilic one by Azan. Although the reactive area with anti CC9 antibody showed relatively weak in the cytoplasm by anti eNOS antibody and no in the nucleus of cardiocytes with anti RBM3 antibody, outside of the reactive area with anti CC9 antibody there were intensive reactivity with anti eNOS antibody in cytoplasm and in a nucleus with anti RBM3 antibody. Anti HIF1 antibody showed weak reactivity with cytoplasm of endocardial cardiocytes and no with cytoplasm of cardiocytes in another area. The results obtained from the present cases revealed that the hypoxic change was equivalent even though the cause of cardiomegaly was deferred between two cases, and conventional staining such as HE and Azan utilized to detect hypoxic change in the heart and immunohistochemical studies seemed to be a useful tool for clarifying the cascade of hypoxic changes in the myocardium.
Satoshi Furukawa1,2*, Mayumi Kataoka1 , Satomu Morita1,2, Akari Uno2 , Masahito Hitosugi2 , Hiroshi Matsumoto1,3 and Katsuji Nishi1,2
A 45-year-old woman with multiple sclerosis was admitted to our hospital after out of hospital cardio-pulmonary resuscitation. The first ECG showed ventricular fibrillation. Following direct current defibrillation and mechanical reanimation, spontaneous circulation was restored and the ECG unremarkable without any signs of ischemia. Coronary angiography showed unobstructed coronary arteries Figure 1, (Panel A). Left ventriculography revealed apical wall obstruction, suggestive of apical aneurysm (Panel B, supplementary videos). Transthoracic echocardiography and Cardiac Magnetic Resonance Imaging (CMR) eventually lead to the diagnosis of a rare case of Apical Hypertrophic Cardiomyopathy (AHC) with ace of spades-form (Panel C,D). The patient underwent Cardioverter-Defibrillator Implantation (ICD) and amiodarone medical therapy for secondary prophylaxis. Patient’s family history and screening for HCM were unsuspicious.
Wiedemann S# *, Heidrich FM# , Speiser U and Strasser RH