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Strategies for managing behavioral and cognitive symptoms

Click here for full copy of this article >>Caregiver strategies for managing behavioral and cognitive symptoms

The purpose of this paper is to describe a variety of clinical features and challenging situations that may occur. Recent practice parameters focusing on the cognitive and behavioral features of ALS point to a lack of controlled studies on effective management of these symptoms. By incorporating clinical examples, the article reviews salient issues involved in care planning along with strategies aimed at minimizing the negative impact of behavioral, emotional, and cognitive symptoms.

University of Sydney Department of Medicine

Concord Hospital NSW 2139

Molecular Medicine Laboratory

Anzac Research Institute

www.anzac.au

Garth A. Nicholson, MBBS. PhD, FRACP
Professor of Neurogenetics
Clinical Sciences Building
Concord Hospital

Telephone: (02) 9767 6797
Facsimile: (02) 9767 6194
Overseas Fax: 61-2-9767 6194

February 2009

Information on research to identify new genes which can cause motor neurone disease

Professor Garth Nicholson and a research team at the Molecular Medicine Laboratory, Department of Medicine, Sydney University at Concord Hospital are carrying out research to locate genes causing Motor Neurone Disease (MND) and to study how known gene mutations cause the disease.There is no known cause for the majority of motor neurone disease cases, which are isolated (or sporadic). Alternatively, 10% -15% of families with MND has more than one affected person. Some of these families have a gene defect called the SOD1 mutation, which we can detect. Our current research is aimed at locating and mapping new MND gene mutations. If more genes for MND can be found, and the mechanisms of these genes discovered, it is hoped that this will lead to treatment strategies for sufferers of both the familial and sporadic forms of motor neurone disease.

Research into the cause of motor neurone disease is being conducted worldwide, and any new overseas

discoveries would also be immediately applied to the families on our register. Approximately 80% of MND families who do not have the SOD1 mutation provide an impetus for continued search for further MND gene mutations. If your family has had more than one person with MND you can help our research. Participation in the project is likely to benefit future generations rather than provide any immediate benefit to any family member currently affected.

Participation is voluntary. It involves the donation of a blood sample to be stored indefinitely and included in current and future DNA research into motor neurone disease. Individual details are confidential and no individual results of the research are available. Only group results are published in the medical and the scientific literature.

If you wish to support our research into MND by making a donation this can be arranged through the ANZAC website. If you have any questions, or would like to participate in our research please see our website or contact:

www.anzac.edu.au or by contacting us.

Carolyn Cecere Phone: (02) 9767 7016

Research Assistant

Molecular Medicine Laboratory Email: ccecere@anzac.edu.au

Clinical Sciences Building 20A

Concord Hospital

CONCORD NSW 2139 Website: www.anzac.edu.au/index.php?section=48

Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells. [Review]

Source: Cellular & Molecular Life Sciences. 67(22):3837-47, 2010 Nov.

Unique Identifier 20668908

Authors: Nizzardo M. Simone C. Falcone M. Locatelli F. Riboldi G. Comi GP. Corti S.

Institution: Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, Istituto di Ricovero e Cura a Carattere Scientifico Foundation, Milan, Italy. monica.nizzardo@unimi.it

Abstract:

Motor neuron diseases (MNDs) are a group of neurological disorders that selectively affect motor neurons. There are currently no cures or efficacious treatments for these diseases. In recent years, significant developments in stem cell research have been applied to MNDs, particularly regarding neuroprotection and cell replacement. However, a consistent source of motor neurons for cell replacement is required. Human embryonic stem cells (hESCs) could provide an inexhaustible supply of differentiate cell types, including motor neurons that could be used for MND therapies. Recently, it has been demonstrated that induced pluripotent stem (iPS) cells may serve as an alternative source of motor neurons, since they share ES characteristics, self-renewal, and the potential to differentiate into any somatic cell type. In this review, we discuss several reproducible methods by which hESCs or iPS cells are efficiently isolated and differentiated into functional motor neurons, and possible clinical applications.

Nutritional factors associated with survival following enteral tube feeding in patients with motor neurone disease.

Source: Journal of Human Nutrition & Dietetics. 23(4):408-15, 2010 Aug.

Unique Identifier 20487174

Authors: Rio A. Ellis C. Shaw C. Willey E. Ampong MA. Wijesekera L. Rittman T. Nigel Leigh P. Sidhu PS. Al-Chalabi A. Department of Nutrition & Dietetics, King’s College Hospital, London SE5 9RS, UK. a.rio@nhs.net

Abstract:

BACKGROUND: Motor neurone disease (MND) is a progressive neurodegenerative disease leading to limb weakness, wasting and respiratory failure. Prolonged poor nutritional intake causes fatigue, weight loss and malnutrition. Consequently, disease progression requires decisions to be made regarding enteral tube feeding. The present study aimed to investigate the survival, nutritional status and complications in patients with MND treated with enteral tube feeding. METHODS: A retrospective case note review was performed to identify patients diagnosed with MND who were treated with enteral tube feeding. A total of 159 consecutive cases were identified suitable for analysis. Patients were treated with percutaneous endoscopic gastrostomy (PEG), radiologically inserted gastrostomy (RIG) or nasogastric feeding tube (NGT). Nutritional status was assessed by body mass index (BMI) and % weight loss (% WL). Serious complications arising from tube insertion and prescribed daily energy intake were both recorded.
RESULTS: Median survival from disease onset was 842 days [interquartile range (IQR) 573-1263]. Median time from disease onset to feeding tube was PEG 521 days (IQR 443-1032), RIG 633 days (IQR 496-1039) and NGT 427 days

(IQR 77-781) (P = 0.28). Median survival from tube placement was PEG 200 (IQR 106-546) days, RIG 216 (IQR 83-383) days and NGT 28 (IQR 14-107) days. Survival between gastrostomy and NGT treated patients was significant (P < or = 0.001). Analysis of serious complications by nutritional status was BMI (P = 0.347) and % WL (P = 0.489). CONCLUSIONS: Nutritional factors associated with reduced survival were weight loss, alnutrition and severe dysphagia. Serious complications were not related o nutritional status but to method of tube insertion. There was nodifference in survival between PEG and RIG treated patients.

Preserving nerve cells in Motor Neurone Disease

Published: Monday, September 20, 2010 – 11:43 in Health & Medicine

A team of researchers, led by Scott Oakes, at the University of California, San Francisco, has identified a way to prevent symptom onset, weight loss, and paralysis and extend survival in a mouse model of amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig’s disease), providing a new avenue of research for the development of therapeutics for ALS and other motor neuron diseases.

ALS and other motor neuron diseases are neurological disorders that selectively affect nerve cells that control voluntary muscle activities such as speaking, walking, breathing, swallowing, and general movement of the body.

A key feature of these diseases is that the affected nerve cells (which are known as motor neurons) die by a process known as apoptosis.

Determining whether this death contributes to disease or occurs after the nerves have stopped functioning is important to establishing whether blocking apoptosis would have therapeutic benefit.

In the study, genetically eliminating activation of the mitochondrial apoptotic pathway in a mouse model of ALS was shown to preserve motor neuron viability and function, thereby preventing symptom onset, weight loss, and paralysis and extending survival. The authors therefore suggest that inhibiting activation of the mitochondrial apoptotic pathway might provide a way to preserve motor neurons in individuals with ALS and other motor neuron diseases.

Source: Journal of Clinical Investigation

A university of Otago neuroscientist has helped unlock the secrets of a protein that may alleviate the symptoms of debilitating and deadly motor neurone disease.

Associate Professor Ian McLennanAssoc Prof Ian McLennan and Aberdeen University researcher Dr Guy Bewick have found a hidden mechanism that regulates how brain cells talk to each other. They discovered a protein known as transforming growth factor beta 2, regulates how motor neurones send signals to neighbouring cells – and they want to find ways to use it.

Prof McLennan said targeting the mechanism might lead to new therapies for the symptoms of motor neurone disease, which affects up to 250 New Zealanders at any one time. Previous work on how the protein worked in brain stems showed it relieved the early symptoms of the disease in mice. However, it was known to be highly toxic to people. The “surprising” breakthrough, which was about five years in the making, “unlocked the door to how the protein worked”. It meant researchers could concentrate on using the signalling system to find non-toxic therapies, he said.

Prof McLennan cautioned any therapy that could come from the findings would fall short of a cure for motor neurone disease. But it may be able to alleviate symptoms during the early stages of the condition.

Motor neurone disease is a catch-all description for three different disease types. Their symptoms include fatigue, muscle weakness, tightness and wasting, twitching, slurred speech and inexplicable choking. Sufferers usually die after a progressive weakening of their respiratory system, which usually happens over a couple of days.

It is most prevalent in people aged 40-70.

On average, sufferers live for between two and four years with the disease.

Prof McLennan and Dr Bewick’s findings have been published in the United States journal Proceedings of the National Academy of Sciences.

The study was supported by the Marsden Fund of New Zealand.

Reported by Stu Oldham in the Otago Daily Times 14/07/2010