**12. Management of motor neuron disease (MND)**

#### **12.1 Investigations**

There are no specific investigations for MND. Till now there are no specific biochemical or pathological markers of MND. The aim of Elctrophysiological, Imaging and laboratory investigations is to exclude MND mimics and/ or to support clinical signs presented by the patients.

Allum and Shaw (2010) clarified that investigations are important adjuncts to the clinical diagnosis of MND. Properly used they can provide supportive evidence of the clinical findings and help delineate the extent of disease. Investigations are also important to identify benign or treatable MND mimics.

#### **12.2 Treatment plan of motor neuron disease**

Although MND is still incurable disease up till now, in the last two decades MND management has evolved rapidly. Symptomatic treatment of MND still had the upper hand of management plan, especially for respiratory and bulbar complications. A team of work including neurologist, highly qualified nurses, ICU specialist in respiratory complications, psychologist, dietition, physiotherapy and speech therapist must be involved for management plan and follow up of MND patients, table (5).

Thus treatment strategy of MND was aimed towards;


Motor Neuron Disease 213

management, initation of respiratory and nutritional interventions, unbiased information regarding research

practical advice regarding accessing support services, patient

safety awareness, adaptive and splinting devices, activity modification, driving, energy conservation, home modification

management of dysphagia, management of enteral feeding

Evaluation and management of cognitive impairment/dementia,

Evaluation and monitoring of dysphagia and aspiration, speech therapy and counseling regarding communication devices

**Neurologist** Diagnosis, disclosure of diagnosis, treatment and symptom

**Family Doctor** Symptom control, drug monitoring, liaison with other teams **ALS Specialist Nurse** Liaison with medical team and coordination of care, home visits,

**Occupational Therapist** Optimization of the patient's environment. Advice regarding

**Dietitian/Nutritionist** Evaluation of nutritional status and the need for tube feeding,

**Physiotherapist** Evaluation of muscle strength and function, advice regarding

life, preservation of dignity

walking aids and orthoses, safety awareness **Social Worker** Advice and control, pain management, maintenance of quality of

adjustment disorders, anxiety and depression **Respiratory Physician** Assessment of respiratory dysfunction, initiation of non-invasive

Riluzole (2-amino-6-(trifluoromethoxy) benzothiazole, RP 54274) is the only drug licensed to treat ALS. Although the drug reduces glutamate-induced excitotoxicity, its précis mechanism in ALS is unknown. A Cochrane Library meta-analysis (including three doubleblind randomized placebo controlled trials by (Miller, 2002) suggests that riluzole provides a 9% gain in the probability of surviving one year and adds approximately 2 months to

Ability to interfere with intracellular events that follow transmitter binding at excitatory

developments

advocacy

ventilation

Table 6. Roles of the multidisciplinary team\* with permission

**Riluzole, exerts the following pharmacologic effects:** 

Inactivation of Voltage – dependent sodium channels.

amino acid receptor (Riluzole monograph 2011).

An inhibitory effect on glutamate release.

**Speech & Language** 

**Therapist** 

**Psychiatry and Neuropsychology** 

\* (phukan and Hardiman, 2009)

1. pharmacological 2. symptomatic and

patient survival.

**12.3 Different types of treatment** 

3. treatment of complications

**12.3.1 Pharmacological treatment** 


Table 5. Investigatory Tools for MND

 Active denervation (positive sharp waves, fibrillation potentials, Fasciculation

evidenced by large motor unit potentials (Allum and Shaw

Abnormal Jitter and blocking of neuromuscular trans -mission (Leig Ray – chaudhuri 1994)

 Normal in early stages of ALS. In advanced disease the

> compound muscle action potential amplitude

 Abnormal SCV should raise suspicion of an alternative diagnosis (Eisen. 2001)

Typically normal

According to diagnosed neurological disorders

Normal

Normal

becomes reduced, indicating denervation (Daube. 2000)

Potentials)

2010)

Chronic denervation

help in diagnosis of ALS by establishing the Presence of

involvement (Eisen and

Reflect early reinnervation and collateral sprouting and may provide evidence of A.H.C. damage in normal muscles (Leigh Ray

subclinical LMN

– chaudhuri 1994)

mimic ALS

demyelinating

compression

2009)

neuropathies (Eisen. 2001)

To exclude cord and root

To exclude infiltrative lesion of tongue and pharynx (Turner, et al,

To exclude MND minics as



Swash. 2001)

**Types of investigatory Tools Aim Findings** 

Electromyography Identification of LMN loss

**Motor conduction Velocity** To exclude disorders that

**Sensory conduction velocity** Differentiating ALS From

**I- Electrophysiology** 

 Single fibre EMG, macro EMG and central motor conduction using magnatic stimulation

**Nerve conduction studies** 

 MRI spine for Limb onset ALS without bulbar manifestation

> presented by bulbar manifestation

 Routine investigations (complete blood count, liver, kidney and thyroid function tests, Blood sugar curve electrolyte, calcium,

Table 5. Investigatory Tools for MND

MRI brain for ALS

**III- laboratory investigations** 

CK----- etc

**II-Imaging** 


\* (phukan and Hardiman, 2009)

Table 6. Roles of the multidisciplinary team\* with permission

#### **12.3 Different types of treatment**


#### **12.3.1 Pharmacological treatment**

Riluzole (2-amino-6-(trifluoromethoxy) benzothiazole, RP 54274) is the only drug licensed to treat ALS. Although the drug reduces glutamate-induced excitotoxicity, its précis mechanism in ALS is unknown. A Cochrane Library meta-analysis (including three doubleblind randomized placebo controlled trials by (Miller, 2002) suggests that riluzole provides a 9% gain in the probability of surviving one year and adds approximately 2 months to patient survival.

#### **Riluzole, exerts the following pharmacologic effects:**


Motor Neuron Disease 215


Tricyclic antidepressant Selective serotonin-reuptake inhibitors (Iannaccone and Ferini, 1996) Levodopa Dextrometorphan and quinidien (Brooks, et al, 2004)

Lorazepam Reassurance

Comfort (seating, sleeping, day and night care)

Speaking techniques (Murphy, 2004) Voice amplifiers Brain-computer interfaces (Kübler et

Hydration Increased

Comfort, analgesia

Psychological support, counseling

al 2001)

Modafinil (Bradly et

al, 2005)

Amitriptyline Citalopram Psychological support

fiber intake

counseling

Baclofen

drugs - Opioids

Lactulose Senna

Amitriptyline Zolpidem


Table 7. Symptomatic treatment of Motor Neuron Disease. Modified From Radunovic et al

Corticospinal tract

damage (pseudobulbar syndrome)

sensitivity

stiffness

Pseudobulbar syndrome

**Laryngospasm** Pharyngeal

**Pain** Immobility,

**Constipation** Immobility;

**Depression** - Hopelessness;

**Insomnia** Discomfort, pain,

**Fatigue** - Muscle weakness

2007 and leigh et al 2003


opiates, Dehydration


frustration

depression; (consider respiratory insufficiency)

**Anxiety** Many Factors - Lorazepam

**Excessive or violent yawning**

**Emotional lability** 

**Communication difficulties** 

	- Elevation in liver transaminases. Regular monitoring of liver function is advised (every month for 3 months, every 3 months for a further nine months then annually thereafter).
	- Rare cases of neutropenia have been reported. White cell count must be checked in the case of febrile illness

**Contraindications-**Renal and hepatic impairment Pregnancy and breast-feeding (Brockington and Shaw, 2003)

#### **12.3.2 Symptomatic treatment**


**Side Effects** Nausea and vomiting, Asthenia, somnolence Headache, dizziness, and

 Elevation in liver transaminases. Regular monitoring of liver function is advised (every month for 3 months, every 3 months for a further nine months then annually

Rare cases of neutropenia have been reported. White cell count must be checked in

Carbamazepine Phenytion Magnesium (Miller, et al, 1999;

Physiotherapy Physical exercise

Hydrotherapy (Miller, et al, 1999; Andersen,

Physiotherapy (Millul

Home suction device

(Andersen, et al, 2005)

botulinum toxin into parotid glands (Giess

Home suction device hydrobromide (Miller, et al,

1999/Andersen, et al, 2005) Reduced intake of diary products, alcohol, and caffeine.

Massage

et al, 2005)

et al, 2005) Hydrotherapy Cryotherapy

Nebulisation

injections of

et al, 2000/ Winterholler et al, 2001) irradiation of the salivary glands (Iannaccone et al, 1996; Stalpers and Moser, 2002)

Andersen, et al, 2005)

Baclofen Tizanidine

Restivo et al, 2002)

Bulbar weakness Atropine Hyoscine

2001)

1996)

Dantrolene Botulinum toxin type A (Wnterholler et al,2002 ;

hydrobromide (Miller, et al, 1999; Andersen, et al, 2005) Amitriptyline (Bradley et al,

Carbocisteine Propranolol Metoprolol (Newall, et al,

**Contraindications-**Renal and hepatic impairment Pregnancy and breast-feeding

**Symptom Cause Drugs Other treatment** 

**Dosage** 50mg twice daily

Serious Adverse Effects

thereafter).

(Brockington and Shaw, 2003)

**12.3.2 Symptomatic treatment** 

**Cramps** Changes in motor

**Spasticity** Corticospinal tract damage

**Exessive watery**

**Persistent saliva and bronchial secretions** 

**Saliva** 

function


the case of febrile illness

vertigo


Table 7. Symptomatic treatment of Motor Neuron Disease. Modified From Radunovic et al 2007 and leigh et al 2003

Motor Neuron Disease 217

Abrahams S., Goldstein L.H., Simmons A., et al. (2004). World retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Brain;127:1507-17 Allum C.W,& Shaw P. (2010). Motor neurone disease: a practical update on diagnosis and

Andersen P.M., Borasio G.D., Dengler R., et al. (2005). EFNS task force on management of

Andersen P.M., Sims Xin W.W., et al. (2003). Sixteen novel mutations in the Cu/Zn

Bak T.H.,& Hodges J.R.& (2004). The effects of motor neuron disease on language: further

Baltadzhieva R., Gurevich T.,& Korezyn A.D. (2006). Autonomic impairment in

Bourke S.C., Shaw P.J.,& Gibson G.J. (2001). Respiratory function vs sleep-disorderd

Bradley W.G., Anderson F., Bromberg M., et al. (2001). Current management of ALS:

Brockington A.,& Shaw P. (2003). Developments in the treatment of Motor Neurone Disease.

Brooks B.R. (1994). EL Escorial World Federation of Neurology criteria for the diagnosis of

Brooks B.R., Thisted R.A., Appel S.H., et al. (2004). Treatment of pseudobulbar affect in ALS

Brugman F., & Wokkle J.H.J. (2004). Primary Lateral Sclerosis. Orphanet Encyclopedia.

Carter G.T., Weiss M.D., Lou J.S., et al. (2005). Modafinil to treat fatigue in amyotrophic lateral sclerosis: an open label pilot study. Am J Hosp Palliat Care;22:55-59.

Daube J.R. (2000). Electrodiagnostic studies in amyotrophic lateral sclerosis and other motor

De Domenice P., Malara C.E., Marabello L., et al.( 1988). Amyotrophic lateral sclerosis; an

Duffy J.R., Peach R.K., & Strand E.A. (2007). Progressive apraxia of speech as a sign of motor

epidemiological study in the Province of Messina, Italy, 1976-1985.

with dextromethorphan/quinidine, Neurology;63:1363-70.

April, http://www.orpha.net/data/patho/GB/uk-PLS.bdf.

Cleveland D.W.& Rothstein. J.D. (2001). Nat. Rev Neurosci 11,806-819.

neuron disorders. Muscle Nerue; 23:1488-502.

neuron disease. Am J Neuroradial;16:198-208.

comparison of the ALS CARE Database and the AAN Practice Parameter.

amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Disease/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Disease and El Escorial " Clinical limits of amyotrophic lateral sclerosis" workshop contributors. J Neurol Sci 124:96-107. Brooks B.R., Miller R.G., Swash M. & Munsat T.L. (2000). World Federation of Neurology

Research Group on Motor Neuron Disease: El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic Lateral Scler. Other

amyotrophic lateral sclerosis. Curr Opin Neurol;18:487-93.

breathing as predictors of Qol in ALS. Neurology 57:2040-2044.

amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients

superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph Lateral Scler Other Motor Neuron

management. Clinical Medicine, Vol 10. No 3: 252-8

and relatives. Eur J Neurol;12:921-38.

evidence. Brain Lang;89:354-61.

Acnr. Vol 3 N 5 November/December.

Motor Neuron Disord, 1:293-239.

Neuroepidemiology;7:152-8.

Disorders;4:62-73.

Neurology;57:500-04.

**14. References** 
