Supporting people with Motor Neuron Disease (MND) to make decisions about gastrostomy feeding tube placement: a survey of UK healthcare professionals' practice and beliefs.

OBJECTIVE: Understand the practice and beliefs of healthcare professionals (HCPs) supporting the decision-making of people with MND (pwMND) about gastrostomy placement, including identifying differences between professions. METHODS: An online cross-sectional survey disseminated to HCPs who support the decision-making of pwMND about gastrostomy placement. RESULTS: A total of 139 participants completed the survey including representation from a range of healthcare professions. A third (36/101, 36%) initiated discussions about gastrostomy later in practice than they believed was ideal. In relation to the outcome of declining compared to accepting gastrostomy, participants were more likely to discuss aspiration (80% vs. 68%), choking (76% vs. 58%) and prognosis (36% vs. 22%). Participants believed gastrostomies should be placed after a mean 8.1% weight loss since symptom-onset. More participants favored gastrostomy placement before pwMND presented with respiratory symptoms (45%) compared to onset of dysphagia (11%). Half believed pwMND placed gastrostomies too late. Participants were more likely to 'often'/'always' recommend pwMND to have a gastrostomy (23%) than continue without (7%) or decline (4%) gastrostomy, when believing these were the best option for pwMND. Nurses and dietitians discussed the broadest range of information, while doctors were more likely to discuss mortality risk and prognosis. CONCLUSION: There is variation in HCPs practice and beliefs about initiating discussions, the sharing of information and recommendations, and timing, about gastrostomy placement. The information shared varies by profession and there is evidence of sub-optimal communication between HCPs. Further research is required to understand how these findings may impact on the decision-making of pwMND about gastrostomy.

Surgical Treatment for Spasticity: Selective Dorsal Rhizotomy ­ Technique and Literature Review

Spasticity is amotor disorder that leads to a resistance to passive jointmovement. Cerebral palsy is the most important cause of spasticity and can be caused by several factors, including multiple gestations, alcoholism, infections, hemorrhages, drowning, and traumatic brain injuries, among others. There aremany scales that help tomeasure andmonitor the degree of impairment of these patients. The initial treatment should focus on the causal factor, such as tumors, inflammation, degenerative diseases, hydrocephalus, etc. Subsequently, the treatment of spastic musculature includes oral or intrathecal myorelaxants, spinal cord electrostimulation, neurotomies, Lissauer tract lesion, dentatotomy and selective dorsal rhizotomy. The latter is a safetechnique, possibleto beperformed inmost centers with neurosurgical support, and it is effective in the treatment of severe spasticity. In this article, the authors describe the surgical technique and conduct a review the literature.

Gastrostomy uptake in motor neurone disease: a mixed-methods study of patients' decision making.

OBJECTIVES: Gastrostomy decision making is a complicated, multifaceted process for people with motor neuron disease (MND). This study explored demographic and disease-related factors that may impact on gastrostomy uptake; and reasons why people with MND accepted or declined gastrostomy, with a focus on how perceptions of swallowing and nutrition may influence decision making. DESIGN: Prospective, cross sectional, mixed methods. SETTING: An Australian multidisciplinary, specialty MND Service. PARTICIPANTS: 33 patients were recommended gastrostomy by the treating medical specialist. 16 of 33 were invited to participate in the prospective decision making study; of whom 10 provided informed consent. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographic and disease-related factors contributing to uptake are described. A stepped approach was applied to gain a comprehensive understanding of why people with MND accept or decline gastrostomy. Instruments included standardised assessments, nutrition survey and semistructured interview. Data were collected at three separate appointments, spanning a 3-week period. RESULTS: Gastrostomy uptake was 73% following medical specialist recommendation. Participants took days, weeks or months to consider their preferences, with lengthy hospital waiting times for the procedure. Gender, site of onset and rate of disease progression were observed to contribute to uptake. Age and symptom duration did not. Integration of quantitative and qualitative data suggests that patient perceptions of swallowing and nutrition contribute to gastrostomy acceptance; however, the decision making process is heterogeneous and these factors may not be the sole or primary reasons for acceptance. Other reported factors included: reducing carer burden, improving quality of life, increasing independence, continuing participation in social outings and gaining control. CONCLUSIONS: Future research may give greater insight into how healthcare organisations can better facilitate gastrostomy decision making, to meet the needs of people living with MND. Larger, prospective, multisite studies may build on these findings to better inform clinical guidelines and minimise the impacts of delayed gastrostomy insertion.

Improved survival and 30-day mortality after gastrostomy in Scottish motor neurone disease patients: evidence from a national retrospective cohort study using STROBE criteria.

Objectives: Defining historical changes and outcomes in the use of gastrostomy in the management of Scottish MND patients. Methods: The 1989-1998 and 2015-2016 Scottish national MND cohorts were used to examine the frequency, timing, and survival related to gastrostomy. The cohorts were censored for survival analysis. Results: There were 261 cases, 119 (46%) from the new register (2015-2016) and 142 (54%) from the old register (1989-1999). Percutaneous endoscopic gastrostomy (PEG) tubes were used exclusively in the old register vs. the new register where PEG (45%), Radiologically inserted gastrostomy (RIG) (44%) and a small number of peroral image-guided gastrostomy (PIGG) tubes (11%), p < 0.01 were used. Odds of 30-d mortality in the old register were 2.8 times that in the new register, p < 0.01. Median survival time from gastrostomy was significantly higher in the new register, 2.7 months, p < 0.05. Median survival time from onset was also higher in the new register but non-significant, 3.2 months, p = 0.30. Multivariate analysis identified age at onset (hazard ratio [HR] 1.02 p = 0.01), time from onset to diagnosis (HR 0.74 p < 0.01), subtype of onset (HR 1.52 p = 0.01), with gastrostomy and Riluzole interacting as variables that predict risk of death. Conclusions: Gastrostomy use has increased with techniques changing over time. It is safer and survival time has increased post gastrostomy. Being older and diagnosed more quickly increases risk of death whilst taking Riluzole combined with gastrostomy reduced risk of death. Survival from onset has not significantly changed in Scottish MND patients having gastrostomy.

Surgical Management of Upper Extremity Deformities in Patients With Upper Motor Neuron Syndrome.

Injury to the central nervous system can create upper extremity deformities and dysfunction, typically caused by a cerebrovascular accident, traumatic brain injury, anoxic brain injury, or spinal cord injury. Regardless of the etiology, disruption of inhibitory upper motor neuron (UMN) pathways can lead to a constellation of symptoms such as muscle weakness, decreased motor control, hyperexcitable tendon reflexes, muscle spasticity, and agonist-antagonist cocontraction that characterizes a condition known as UMN syndrome. The magnitude of neurorecovery varies among patients who have sustained brain injuries and can be classified as having a functional or nonfunctional upper extremity based on the presence or absence of volitional motor control at a specific joint, respectively. Many surgical procedures can be employed to optimize function, decrease pain, improve hygiene, and enhance cosmesis in patients with UMN syndrome.

The Neuro-Orthopaedic Approach.

Upper motor neuron disease or injury can lead to muscle spasticity or nonfunction throughout the body. Imbalance in muscle forces predisposes patients to development of functional deficiencies, contractures, pain, and poor hygiene. The approach to neuro-orthopaedic patients is by necessity multidisciplinary, because a variety of nonsurgical and surgical options are available. In evaluating each patient, surgeons must consider the extent and quality of any deformity, potential for improvement in function, the ability to alleviate pain, and potential for improvement in hygiene and cosmesis. Surgical techniques include tendon lengthenings, releases, transfers, osteotomies, and bony fusions.

Tracheostomy and salivary gland radiotherapy for severe sialorrhoea in motor neurone disease.

The management of excessive secretions in patients with motor neurone disease can be challenging. In this paper, we highlight the main issues from the perspectives of a patient, specialist nurse and neurologist and the importance of a multidisciplinary approach.

Bulbar dysfunction in normal pressure hydrocephalus: a prospective study.

OBJECTIVE Normal pressure hydrocephalus (NPH) is clinically characterized by gait disturbance, cognitive impairment, and urinary incontinence, as well as enlargement of the ventricles. To the best of the authors' knowledge, there have been no previous publications regarding the correlation between bulbar dysfunction and NPH. The primary objective of this study was to compare preoperative and postoperative prevalence of bulbar dysfunction in patients with NPH. Secondary objectives included assessing the results of surgery for swallowing, speech, gait, cognition, and urination, and evaluating the correlation between bulbar dysfunction and triad symptoms. METHODS Fifty-three patients with NPH who underwent shunt placement surgery at Siriraj Hospital were included in the study. Patients were evaluated for gait, cognition, urination, swallowing, and speech before and 6 months after shunt placement. Triad symptoms were assessed using standard methods. Bulbar dysfunctions were assessed using the Swallowing Problem Questionnaire, Thai Articulation Test, Resonation Screening Test (RST), and Thai Nasality Test. The Thai Speech Assessment Program and nasometer were used for objective speech measurement. RESULTS Preoperatively, 86% (43/50) of patients had swallowing problems and 75% (37/49) had speech problems, as measured by the RST. Postoperatively, there was significant improvement in swallowing (p < 0.001), speech problems by RST (p = 0.008), and voice volume (p = 0.009), but no significant change in the nasometer test. All triad symptoms were improved. There were significant correlations between swallowing impairment and gait disturbance (r = 0.358, p = 0.009), and RST and cognitive impairment (r = -0.502, p < 0.001). CONCLUSIONS This is the first study of bulbar dysfunction in patients with NPH. The results showed that the prevalence of bulbar dysfunction is very high. The correlation between bulbar dysfunction and the classic NPH triad has been documented and published. These bulbar symptoms also significantly improved after surgery. As such, bulbar dysfunction should be regarded as a core symptom that should be considered along with the classic triad in the clinical diagnosis and management of NPH.

The impact of gastrostomy in motor neurone disease: challenges and benefits from a patient and carer perspective.

OBJECTIVES: This study explores the experience of gastrostomy insertion from the perspective of the patients and their informal carers. Gastrostomy feeding is commonly used to support motor neurone disease (MND) patients with dysphagia. However, there is lack of information describing patient and carer experiences following gastrostomy insertion. The effect of gastrostomy on quality of life for these patients and their family is currently not well understood. METHODS: Retrospective qualitative exploration using semistructured interviews with patients and their informal carers to elicit in-depth descriptions of their experiences and views following gastrostomy. RESULTS: 27 patients consented to the study; of these, 23 underwent a successful gastrostomy. 10 patients and 8 carers were interviewed, approximately 3 months following a successful gastrostomy. Participants described clinical complications, practical issues, time restrictions imposed by strict feeding regimens and psychological issues, which adversely impacted on quality of life. However, the establishment of a safe alternative route for feeding and medication, and the reduced worry over difficult meals and weight loss, were described by all as outweighing these negative impacts. Participants also described having received education/training on gastrostomy feeding both in hospital and in the community, which helped them to cope during the transition from oral to gastrostomy feeding. CONCLUSIONS: This study highlights the challenges and benefits of gastrostomy as well as the importance of education and information provision. Emphasis should be given to education before and after insertion along with support and care in the community. While the significant impact of gastrostomy on patients and carers should not be underestimated, the potential benefits were described as outweighing these concerns.

A rare case of tuberculosis with motor neuron disease.

Motor neuron disease (MND) is occasionally aggravated by chronic infection. A misdiagnosed case of tuberculosis with MND is illustrated in a 45-year-old woman who underwent successful VATS wedge excision, which is presented herein. MND in an adult is a rare clinical entity. In order to facilitate the preoperative diagnosis and avoid the misdiagnosis of this disease, more etiological factors need to be considered.

Myotendinous lengthening of the elbow flexor muscles to improve active motion in patients with elbow spasticity following brain injury.

BACKGROUND: The objective of this study was to evaluate the outcomes of a novel technique of fractional myotendinous lengthening of the elbow flexors in patients with volitional motor control and spastic elbow flexion deformities after brain injury. METHODS: A retrospective review of 42 consecutive patients with spastic elbow flexion deformities and upper motor neuron (UMN) syndrome was performed. Each patient had volitional motor control but limited elbow extension and underwent myotendinous lengthening of the elbow flexor muscles. Outcome measures included pre and post-operative active and passive arc of motion, Modified Ashworth Scale (MAS) of spasticity, and complications. RESULTS: There were 26 men and 16 women. The etiologies of UMN syndrome were stroke (30 patients), traumatic brain injury (11 patients), and cerebral palsy (1 patient). Average duration between injury and surgery was 6.6 years. At an average follow-up of 14 months, improvements were noted in active extension (42° to 20°; P < .001). In addition, active arc of motion increased from 77° (range of motion [ROM]: 42° to 119°) to 113° (ROM: 20° to 133°) (P < .001) and passive arc of motion increased from 103° (ROM: 24°-127°) to 131° (ROM: 8°-139°) (P < .001). Significant improvement in MAS was also noted after surgery (2.7 to 1.9; P < .001). Superficial wound dehiscence occurred in 2 patients and was successfully treated nonoperatively. CONCLUSION: In patients with spastic elbow flexion deformities and active motor control, fractional myotendinous lengthening of the elbow flexors safely improves active extension and the overall arc of motion while affording immediate postoperative elbow motion. LEVEL OF EVIDENCE: Level IV, Case Series, Treatment Study.

Gastrostomy use in motor neurone disease (MND): a review, meta-analysis and survey of current practice.

Abstract Gastrostomy feeding is commonly used to support MND patients with dysphagia. In this paper we review three main methods of gastrostomy insertion (PEG, RIG, PIG); conduct a meta-analysis of mortality data following gastrostomy; and present a survey of current practice. A review of the literature revealed a lack of high quality evidence to indicate the optimal method and timing for gastrostomy insertion in patients with MND. A survey of 20 MND clinics demonstrated a clinic-based variability of gastrostomy practices due to factors such as clinician preference, availability of method, and patient respiratory function. The meta-analysis demonstrated that the estimate of the absolute difference in mortality rates was 2.1% higher for PEG (- 6.3%, + 11.2%), suggesting that RIG and PIG methods may be safer than PEG. These results and observations highlight the need for more research to evaluate and compare the safety of the differerent gastrostomy insertion methods in MND care.

Generation of motor neurons from pluripotent stem cells.

Alpha motor neurons (also known as lower or skeletal motor neurons) have been studied extensively for over 100 years. Motor neurons control the contraction of skeletal muscles and thus are the final common pathway in the nervous system responsible for motor behavior. Muscles become paralyzed when their innervating motor neurons die because of injury or disease. Motor neuron diseases (MNDs), such as Amyotrophic Lateral Sclerosis, progressively destroy motor neurons until those inflicted succumb to the illness due to respiratory failure. One strategy being explored to study and treat muscle paralysis due to motor neuron loss involves deriving surrogate motor neurons from pluripotent stem cells. Guided by decades of research on the development of the spinal cord, recent advances in neurobiology have shown that functional motor neurons can be derived from mouse and human embryonic stem (ES) cells. Furthermore, ES cell-derived motor neurons restore motor behavior when transplanted into animal models of motor dysfunction. The recent discovery that mouse and human motor neurons can be derived from induced pluripotent stem (iPS) cells (i.e., somatic cells converted to pluripotency) has set the stage for the development of patient-specific therapies designed to treat movement disorders. Indeed, there is now hope within the scientific community that motor neurons derived from pluripotent stem cells will be used to treat MNDs through cell transplantation and/or to screen molecules that will prevent motor neuron death. In this chapter, we review the journey that led to the generation of motor neurons from ES and iPS cells, how stem cell-derived motor neurons have been used to treat/study motor dysfunction, and where the technology will likely lead to in the future.

Stem cell transplantation for motor neuron disease: current approaches and future perspectives.

Motor neuron degeneration leading to muscle atrophy and death is a pathological hallmark of disorders, such as amyotrophic lateral sclerosis or spinal muscular atrophy. No effective treatment is available for these devastating diseases. At present, cell-based therapies targeting motor neuron replacement, support, or as a vehicle for the delivery of neuroprotective molecules are being investigated. Although many challenges and questions remain, the beneficial effects observed following transplantation therapy in animal models of motor neuron disease has sparked hope and a number of clinical trials. Here, we provide a comprehensive review of cell-based therapeutics for motor neuron disorders, with a particular emphasis on amyotrophic lateral sclerosis.

Meeting report of the International Consortium of Stem Cell Networks' Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis/Motor Neuron Disease.

The International Consortium of Stem Cell Networks' (ICSCN) Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disease (MND) was held on 24-25 January 2011. Twenty scientific talks addressed aspects of cell derivation and characterization; preclinical research and phased clinical trials involving stem cells; latest developments in induced pluripotent (iPS) cell technology; industry involvement and investment. Three moderated panel discussions focused on unregulated ALS/MND treatments, and the state of the art and barriers to future progress in using stem cells for ALS/MND. This review highlights the major insights that emanated from the workshop around the lessons learned and barriers to progress for using stem cells for understanding disease mechanism, drug discovery, and as therapy for ALS/MND. The full meeting report is only available in the online version of the journal. Please find this material with the following direct link to the article: http://www.informahealthcare.com/als/doi/10.3109/17482968.2011.590992 .

Dual transplantation of human neural stem cells into cervical and lumbar cord ameliorates motor neuron disease in SOD1 transgenic rats.

Stem cells provide novel sources of cell therapies for motor neuron disease that have recently entered clinical trials. In the present study, we transplanted human neural stem cells (NSCs) into the ventral horn of both the lumbar (L4-L5) and cervical (C4-C5) protuberance of SOD1 G93A rats, in an effort to test the feasibility and general efficacy of a dual grafting paradigm addressing several muscle groups in the front limbs, hind limbs and the respiratory apparatus. Transplantation was done prior to the onset of motor neuron disease. Compared with animals that had received dead NSC grafts (serving as controls), rats with live NSCs grafted at the two spinal levels lived 17 days longer. Disease onset in dually grafted animals was delayed by 10 days compared to control animals. Disease duration in NSC-grafted animals was longer by 7 days compared to controls. Our results support the potential of NSC grafts at multiple levels of spinal cord as future cellular therapy for motor neuron disease.

Thoracic disk herniation manifesting as sciatica-like pain--two case reports.

Two patients presented with sciatica-like pain caused by thoracic disk herniation. Sciatica-like pain was the initial and major symptom in both patients, but careful neurological examination showed vague signs of upper motor neuron disturbance, and thoracic magnetic resonance (MR) imaging revealed disk herniations at the mid-thoracic level. After video-assisted thoracoscopic discectomy, the pain was completely improved. Thorough neurological examination and MR imagery of the thoracic spine, and if needed, even the cervical spine, are required if lumbar image findings do not correlate with the symptoms or physical examination.

Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells.

Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and ßIII-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 µM) or inhibitor nicotinamide (100 µM). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.