**9. Acknowledgments**

Prof. Garth Nicholson who introduced me to research into motor neurone disease and his continuing support. Prof. David Burke and Assoc. Prof. Alastair Corbett for their professional guidance and Prof. Jasper Daube for his technical assistance regarding the technique used in this research. The research was supported by the Motor Neurone Disease Association of NSW (Northern Region), ANZAC Health and Medical Research Foundation, Motor Neurone Disease Research Institute of Australia Inc. and the Nerve Research Foundation.

### **10. References**


as a method of pre-symptomatic testing of individuals who on genetic testing are SOD1 mutation carriers. Regular follow-up of SOD1 carriers with MUNE may lead to early diagnosis, creating an opportunity for future novel approaches and therapies aimed at

Prof. Garth Nicholson who introduced me to research into motor neurone disease and his continuing support. Prof. David Burke and Assoc. Prof. Alastair Corbett for their professional guidance and Prof. Jasper Daube for his technical assistance regarding the technique used in this research. The research was supported by the Motor Neurone Disease Association of NSW (Northern Region), ANZAC Health and Medical Research Foundation, Motor Neurone Disease Research Institute of Australia Inc. and the Nerve Research

Aggarwal, A. (2009). Motor unit number estimation in asymptomatic familial amyotrophic

Aggarwal, A. (2009). Detection of pre-clinical motor unit loss in familial amyotrophic lateral

Aggarwal, A. & Nicholson, GA. (2001). Normal complement of motor units in asymptomatic

Aggarwal, A. & G, Nicholson. (2002). Detection Of pre-clinical motor neurone loss in SOD1

Al-Chalabi, A., Andersen, P.M., Nilsson, P., Chioza, B., Andersson, J.L., Russ, C., Shaw, C.E.,

Andersen, P.M., Nilsson, P., Keranen, M.L., Forsgren, L., Hagglund, J., Karlsborg, M.,

Azzouz, M., Leclerc, N., Gurney, M., Warter, J,M., Poindron, P. & Borg, J. (1997). Progressive

Beal, M.F. (1996). Mitochondria, free radicals and neurodegeneration. *Curr Opin Neurobiol*. 6:

Beckman, J.S., Carson, M., Smith, C.D. & Koppenol, W.H. (1993). ALS, SOD and

Bensimon, G., Lacomblez, L. & Meiniger, V. (1994). A controlled trial of Riluzole in

Brown, W.F. (1972). A method for estimating the number of motor units in thenar muscles

familial (SOD1 mutation) amyotrophic lateral sclerosis. J*. Neurology, Neurosurgery* 

mutation carriers using motor unit number estimation. *J of Neurology, Neurosurgery* 

Powell, J., Leigh, P.N. (1999). Deletions of the heavy neurofilament subunit tail in

Ronnevi, L.O., Gredal, O., Marklund, S.L. (1997). Phenotypic heterogenicity in motor neurone disease patients with CuZn superoxide dismutase mutations in

motor neuron impairment in an animal model of familial amyotrophic lateral

amyotrophic lateral sclerosis. ALS/Riluzole study group. *N Engl J Med*. 330 (9): 585-

and the changes in motor unit counting with aging*. J Neurol Neurosurg* 

lateral sclerosis. *Supplements to Clinical Neurophysiology.* 60:163-169.

sclerosis. *Supplements to Clinical Neurophysiology.* 60:171-179.

amyotrophic lateral sclerosis. *Hum Mol Genet.*8: 157-164.

*and Psychiatry*. 17 (4), 472-48.

*& Psychiatry.* 73(2):199-201.

Scandinavia. *Brain*. 120:1723-1737.

sclerosis. *Muscle Nerve.*20: 45-51.

peroxinitrate. *Nature.*364: 584.

*Psychiatry*.35: 845-852.

661-666.

591.

preserving motor neurones rather than replacing lost motor neurones.

**9. Acknowledgments** 

Foundation.

**10. References** 


Protection of Motor Neurons in Pre-Symptomatic Individuals Carrying

lateral sclerosis. *Mayo Clin Proc*.51: 537-541.

human diseases. *Med Sci Monit*. 8(9): 210-215.

*Neurology, Neurosurgery and Psychiatry.* 61: 565-572.

animal models. *Clin Neurophysiolo*. 112: 955-964.

motor unit instability. *Suppl Clin Neurophysiol* .60: 135-41

*Muscle Nerve.* 23: 193-197.

1322.

1): 111-116.

390-394.

*Nerve.* 30: 463-9.

5: 1465-1470.

SOD 1 Mutations: Results of Motor Unit Number Estimation (MUNE) Electrophysiology 663

Mulder, D.W., Howard, F.M. Jr. (1976). Patient resistance and prognosis in amyotrophic

Mulder, D.W., Kurland, L.T, Offord, K.P., Beard, C.M. (1986). Familial adult motor neurone

Olney, R.K., Yuen, E.C. & Engstrom, J.W. (2000). Statistical motor unit number estimation:

Radunovic, A., Leigh, P.N. (1996). Cu/Zn superoxide dismutase gene mutations in

Ringel, S.P., Murphy, J.R., Alderson, M.K., Byran, W., England, J.D., Miller, R.G., Petajan,

Robberecht,W. (2000). Oxidative stress in amyotrophic lateral sclerosis*. J. Neuro.* 247 (Suppl.

Rosen, D.R., Siddique, T., Patterson, D., Figlewicz, D.A., Sapp, P., Hentati, D., Donaldson,

Reproducibility and sources of error in patients with amyotrophic lateral sclerosis.

amyotrophic lateral sclerosis: correlation between genotype and clinical features. *J.* 

J.H., Smith, S.A., Roelofs, R.I., Ziter, F., Lee, M.Y., Brinkmann, J.R., Almada, A., Gappmaier, E., Graves, J., Herbelin, L., Mendoza, M., Mylar, D., Smith, P. & Yu, P.(1993). The natural history of amyotrophic lateral sclerosis. *Neurology*. 43: 1316-

D., Goto, J., O'Regan, J.P., Deng, H.X., Rahmani, Z., Krizus, A., McKenna-Yasek, D., Cayabyab, A., Gaston, S., Berger, M., Tanzi, R.E., Halperin, .J.J, Herzfeldt, B., Van den Bergh, R., Hung, W.Y., Bird, T., Deng, G., Mulder, D.W., Smyth, C., Laing, N.G., Soriano, E., Pericak-Vance, M.A., Haines, J., Rouleau, G.A., Gusella, J.S., Horvitz, H.R. & Brown R.H., Jr. (1993). Mutations in Cu, Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. *Nature*.362: 59-62. Shaw, C.E., Enayat, Z.E., Powell, J.F., Anderson, V.E., Radunovic, A., Powell, J.F., Leigh,

P.N. (1998). Mutations in all five exons of SOD1 may cause ALS. *Ann Neurol.* 43:

ALS Consortium. The use of statistical MUNE in multicentre clinical trials. *Muscle* 

Sapp, P., Hung, W.Y., Bebout, J., McKenna-Yasek, D., Deng, G., Horvitz, H.R., Gusella, J.S., Brown, R.H., Jr., Roses, A.D. and Collaborators.(1991). Linage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence

Shefner, J.M. (2001). Motor unit number estimation in human neurological diseases and

Shefner, JM. (2009). Statistical motor unit number estimation and ALS trials: the effect of

Shefner, J.M., Cudkowicz, M.E., Zhang, H., Schoenfiekd, D. & Jillapalli, D. (2004). Northeast

Sica, R.E.P., McComas, A.J., Upton, A.R.M. & Longmire, D. (1974). Motor unit estimations in

Siddique, T. & Deng, H.X. (1996). Genetics of amyotrophic lateral sclerosis. *Human Mol Gen.* 

Siddique, T., Figlewicz, D.A., Pericak-Vance, M.A., Haines, J.L., Rouleau, G.A., Jeffers, A.J.,

small muscles of the hand. *J Neurol Neurosurg Psychiatry.*37: 55-67.

of genetic locus heterogenicity. *N Engl J Med*. 324: 1381-1384.

Needleman, H.L. (1997). Exposure to lead: Sources and effects. *N Engl J Med*. 297: 943-945. Noor, R., Mittal, S., & Iqbal E. (2003). Superoxide dismutase – applications and relevance to

disease: amyotrophic lateral sclerosis. *Neurology.* 38: 511-517.


Hand, C.K. & Rouleau, G.A. (2002). Familial Amyotrophic Lateral Sclerosis. *Muscle Nerve.* 

Hanten, W.P., Chen, W.Y., Austin, A.A., Brooks, R.E., Carter, H.C., Law, C.A., Morgan,

in normal subjects from 20 to 64 years of age. *J. Hand Therapy.* 12(3): 193-200. Haverkamp, L.J., Appel, V., Appel, S.H. (1995). Natural history of amyotrophic lateral

Hentati, A., Pericak-Vance, M.A., Nijhawan, D., Ahmed, A., Yang, Y., Rimmler, J., Hung, W-

Hoagland, R.J., Mendoza, M., Armon, C., Barohn, R.J., Byran, W.W., Goodpasture, J.C.,

Kong, J. & Xu,Z. (1998). Massive mitochondria degeneration in motor neurons triggers the

Kosti, V., Jackson-Lewis, V. & Bilbao, F.D. (1997). Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. *Scienc*e. 227: 577. Leigh, P.N. Amyotrophic lateral sclerosis and other motor neurone diseases. (1997). *Current* 

Li, M., Ona, V.O., Gueng, C., Chen, M., Jackson-Lewis, V., Andrews, L.J., Olszewski, A.J.,

McComas, A.J., Fawcett, P.R.W., Campbell, M.J. & Sica, R.E.P. (1971). Electrophysiological

McComas, A.J. (1971). Functional compensation in partially denervated muscles. *J Neurol* 

McComas, A.J. (1991). Motor unit estimation: Methods, results and present status. *Muscle* 

McComas, AJ. (1995). Motor unit estimation: The beginning. *J Clin Neurophysiol.* 12(6): 560-

Mena, I., Marin, O., Fuenzalida, S., Cotzias, G.C. (1967). Chronic manganese poisoning.

Miller, R.G., Mitchell, J.D., Lyon, M., Moore, D.H. (2007). Riluzole for amyotrophic lateral

Mu, X., He, J, Anderson, M. (1996). Altered expression of bcl-2 and bax mRNA in amyotrophic lateral sclerosis spinal cord motor neurones. *Ann Neurol*. 40: 379.

sclerosis (ALS / motor neuron disease (MND). *Cochrane Database Syst Rev*. 1:

McNeil, D. (1996). Statistical Methods.1st Edition. New York. *Wiley & Sons*; 184.

Clinical picture and manganese turnover*. Neurology*. 17: 128-136.

and caspase-3 in an ALS transgenic mouse model. *Science*. 288: 335-339. Lomen-Hoerth, C. & Slawnych, M.P. (2003). Statistical motor unit number estimation: From

M.K., Sanders, D.J., Swan, C.A. & Vanderslice, A.L. (1993). Maximum grip strength

sclerosis in a database population. Validation of a scoring system and a model for

Y., Schlotter, B., Ahmed, A., Ben Hamida, M., Hentati, F., Siddique, T. (1998). Linkage of a commoner form of recessive amyotrophic lateral sclerosis to

Miller, R.G., Parry, G.J., Petjan, J.H., Ross, M.A. & the Syntex / Synergen Neuroscience Joint Venture rhCNTF ALS Study Group. (1997). Reliability of maximal isometric contraction testing in multicenter study of patients with

onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. *J Neurosci*.

Steig, P.E., Przedborski, S. & Friendlander, R.M. (2000). Functional role of caspase-1

estimation of the number of motor units within a human muscle. *J. Neurology,* 

25: 135-159.

18: 3241-3250.

*Opinion Neuro Neurosurg*. 3: 567.

theory to practice. *Muscle Nerve*. 28: 263-272.

*Neurosurgery and Psychiatry*. 34: 121-131.

*Neurosurg Psychiatry* 34:453-460.

*Nerve*. 14: 585-597.

564.

CD001447.

survival prediction. *Brain*. 118: 707-719.

chromosome 15q15-q22 markers. *Neurogenetics*. 2: 55-60.

amyotrophic lateral sclerosis. *Muscle Nerve.* 20: 691-695.


**29** 

*Italy* 

Paolo Bongioanni

*University of Pisa/NeuroCare onlus* 

**Communication Impairment in ALS Patients** 

**Amyotrophic lateral sclerosis** (**ALS**), also called *Lou Gehrig's disease*, is a rapidly progressive neuromuscular disease that attacks the neurons responsible for controlling voluntary muscles. It belongs to a group of disorders known as *Motor neuron diseases* (*MND*): all these syndromes share a common molecular and cellular pathology comprising degeneration of motor neurons (MNs) in cortex, brainstem and/or spinal cord, and the presence of

ALS prevalence in Western countries ranges from 2.7 to 7.4 per 100,000 (Worms, 2001). In 90 to 95 percent of all patients with ALS (PALS), the disease occurs sporadically (*sporadic ALS*, *sALS*); in 5 to 10 percent there is a family history of ALS (*familial ALS*, *fALS*). Most people developing ALS are between the ages of 40 and 70 years (Haverkamp et al., 1995). The disease is 20% more common in men than in women, although more recent data suggest

The cause of ALS is not known, and it is not clear why ALS strikes some people and not others, but both genetic (Ticozzi et al., 2011) and environmental factors (Callaghan et al.,

In PALS, both the brain upper MNs (UMNs) and the brainstem or spinal cord lower MNs (LMNs) degenerate or die: unable to function, the muscles gradually weaken, waste away, and twitch, leading to a wide range of disabilities. Patients lose their strength and the ability

Approximately 70% of PALS have a *spinal form* of the disease: they present with symptoms which may start either distally or proximally in the upper or lower limbs. Some patients see the effects of the disease on a hand or arm, as they experience difficulty with simple tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock; in other cases, symptoms initially affect one of the legs, and patients experience awkwardness when walking or running, or they notice that they are tripping or stumbling more often. Patients with *bulbar-onset* ALS usually present with dysarthria leading to slow slurred speech or a nasal quality; they may also develop dysphagia for solid or liquids after noticing speech problems; almost all patients with bulbar symptoms complain of sialorrhoea with excessive drooling due to difficulty of swallowing saliva and UMN-type facial weakness, which affects the lower part of the face, causing difficulty with lip seal and blowing cheeks.

characteristic ubiquitin and TDP-43-immunoreactive intraneuronal inclusions.

that the gender ratio may be approaching equality (Logroscino et al., 2008).

2011; Calvo et al., 2010; Ferrante et al., 1997) may play a role.

to move their body, but usually maintain control of eye muscles.

**1. Introduction** 

**Assessment and Treatment** 

*Neurological Rehabilitation Unit - Neuroscience Department,* 

