DIAGNOSIS AND MANAGEMENT OF MOTOR

NEURON DISEASE

L E C T U R E R ADV I S E R :
D R . D O N N Y H A M D A N I H A M I D S P. S

B I M A S E N A A RYA Y U D H A
1102013060
DEFINITION
Motor neuron disorders (MNDs) are a clinically and pathologically
heterogeneous group of neurologic diseases characterized by
progressive degeneration of motor neurons; they include both sporadic
and hereditary diseases. Either or both of the following 2 sets of motor
neurons can be affected:

• Upper motor neurons (UMNs), which originate from the primary

motor cortex of the cerebrum (precentral gyrus) and possess long
axons forming corticospinal and corticobulbar tracts
• Lower motor neurons (LMNs), which originate in the brainstem
(cranial nerve [CN] motor nuclei) and spinal cord (anterior horn
cells) and directly innervate skeletal muscles (Takai,Hidehiro. 2014)
EPIDEMIOLOGY
Prevalence
• 4-6 per 100,000 in most parts of the world. Males are more
commonly affected than females (1.4:1).
• (Leigh P.N. 1991)

Incidence
• Increases after the age of 40 years, peaks in the late 60s and
early 70s, and declines rapidly after that.
• (Logroscino, et al. 2008)

In Indonesia: Rarely disease

ETIOLOGY
ALS PBP PMA PLS

• Sporadic ALS: • Unknown • Unknown • Unknown

Unknown
• Familial ALS:
• Genetic defects:
• (SOD-1)
• FUS
• TAR DNA
binding protein-
43 (TDP-43)
• Cod972

(El Thallawy, Hamdy.2013)

CLASSIFICATION

• There are four main types of MND, each affecting people in different
ways. However, these can have overlapping symptoms, which make it
difficult to give an exact diagnosis.

• The most common form is amyotrophic lateral sclerosis (ALS).

Although other forms may be diagnosed, it is possible they will
progress into the more typical form of ALS.

• (Baumer, Dirk., et al. 2014)

CLASSIFICATION

4 Main Types of MND:

• Amyotrophic lateral sclerosis (ALS)
• Progressive bulbar palsy (PBP)
• Progressive muscular atrophy (PMA)
• Primary lateral sclerosis (PLS
CLASSIFICATION
PATHOGENESIS

• The full pathogenesis of ALS is not well understood

as it has not been fully elucidated by medical research.

• However, several key factors can be noted including: (1)

Genetics, (2) Excitotoxicity, (3) Oxidative stress, (4)
Mitochondrial dysfunction, (5) Impaired axonal transport, (6)
Neurofilament aggregation, (7) Protein aggregation, (8)
Inflammatory dysfunction and contribution of non-neuronal
cells, (9) Deficits of neurotrophic factors and dysfunction of
signaling pathways, and (10) Apoptosis.
PATHOGENESIS
CLINICAL PRESENTATION
• The classic ALS presentation is insidious onset of
symptoms which are progressive, and have a
combination of both upper and lower motor
neuron findings on clinical examination.

• The most common presentation is limb-onset;

bulbar onset accounting for between 30-32.5% of
cases.

(Takai,Hidehiro. 2014)
CLINICAL PRESENTATION
• Lower motor neuron findings include muscle wasting, weakness, and fasciculations.

Muscle wasting Fasciculations

CLINICAL PRESENTATION
• Upper motor neuron findings include spasticity, pathologically brisk reflexes, and weakness in
anti-gravity muscles.

Pathological reflexes Spasticity

CLINICAL PRESENTATION
• Bulbar symptoms can include difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and
subsequent excess saliva (sialorrhea).

• Dysphagia Dysarthria Sialorrhea

DIAGNOSIS
According the revised El Escorial Criteria, the diagnosis of ALS is suggested by the
presence of:

• Lower motor neuron dysfunction by physical, electrophysiological, or

neuropathological examination
• Upper motor neuron dysfunction by clinical examination
• Progression of symptoms or signs over 6 months, as demonstrated by spread within
a region or to other spinal regions

In the absence of:

• Electrophysiological or pathological evidence of other disease processes

Neuroimaging evidence of other disease processes
DIAGNOSIS

Restricted phenotypes of ALS currently recognized include:

Progressive bulbar palsy (PBP)

Flail arm (Vulpian Bernhard) syndrome and Flail leg syndrome
Progressive muscular atrophy (PMA)
Primary lateral sclerosis (PLS)
DIAGNOSIS

• Progressive motor neuron disease that affects only the muscles

Progressive bulbar supplied by bulbar motor nuclei and the corticobulbar pathways.
palsy • To the extent that both upper and lower motor neuron deficits are
discerned, ALS can be diagnosed as above.

Flail arm syndrome

(Vulpian Bernhard • Begin with asymmetric deficits of the arms or legs. When these
syndromes involve at least two body regions, ALS can be diagnosed in
syndrome) and Flail the absence of clear UMN signs
leg syndrome
DIAGNOSIS

• Diagnosed if there is clinical evidence of lower motor disease

in one limb or region and clinical or electrophysiological
Progressive evidence of involvement of an adjacent limb or region.
muscular atrophy • When this syndrome involves at least two body regions, ALS
can be diagnosed in the absence of clear UMN signs

• Begins with upper motorneuron deficits existing in isolation. As

such, ALS cannot be diagnosed.
Primary lateral
• If and when clinical or electrophysiological evidence of
sclerosis involvement of the lower motor neuron in at least one limb or
body region is present, ALS can be diagnosed
DIAGNOSIS

• EMG findings that occur in the presence of ALS

include neurogenic potentials, fibrillation
potentials, positive sharp waves, and fasciculation
potentials.

• Diagnostic sensitivity is increased by the

substitution of fasciculation potentials for
fibrillation potentials.

• However, it must be recognized that the origins

of fasciculations are multiple, and are not always
representative of lower motor neuron disease.
DIFFERENTIAL DIAGNOSIS

ALS:

Other neurodegenerative disorders, such as primary lateral sclerosis

(PLS), hereditary spastic paraparesis (HSP), spinal muscular atrophy
(SMA), and X-linked spinobulbar muscular atrophy (SBMA)

Peripheral neuropathies

Postpolio syndrome (PPS)

Monomeric amyotrophy (also known as Hirayama disease)

(Takai,Hidehiro. 2014)
DIFFERENTIAL DIAGNOSIS

Primary lateral sclerosis:

• UMN-dominant ALS

• Structural spinal cord disorders (compressive lesions

at the foramen magnum or cervical spinal cord), such
as cervical spondylotic myelopathy, Arnold-Chiari
malformation, or tumors

(Takai,Hidehiro. 2014)
DIFFERENTIAL DIAGNOSIS

Proggresive Bulbar Palsy:

• Madras motor neuron disease (MMND)

• Boltshauser syndrome (sensorineural hearing

loss, distal muscular atrophy, and vocal cord
paralysis, which is the only lower cranial
nerve sign).

(Takai,Hidehiro. 2014)
TREATMENT

Thus treatment strategy of MND was

aimed towards;

• Delay Progression of the disease and

prevent further loss of motor
neurons especially in the early stage
of the disease

• Symptomatomatic treatment to
alleviate symptoms of the disease
aiming to maintain quality of life

(El Thallawy, Hamdy.2013)

TREATMENT

• Pharmacological treatment

Riluzole (2-amino-6-(trifluoromethoxy) A Cochrane Library meta-analysis suggests

benzothiazole, RP 54274) is the only drug that riluzole provides a 9% gain in the
licensed to treat ALS. probability of surviving one year and adds
approximately 2 months to patient survival.
TREATMENT

Riluzole, exerts the following pharmacologic

effects:

• An inhibitory effect on glutamate release.

• Inactivation of Voltage – dependent Dosage: 50mg twice daily

sodium channels.

• Ability to interfere with intracellular

events that follow transmitter binding at
excitatory amino acid receptor.
TREATMENT

Serious Adverse Effects:

Side Effects: Nausea
and vomiting, Asthenia,
somnolence Headache,
dizziness, and vertigo
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).

Contraindications: Renal and

hepatic impairment Pregnancy
and breast-feeding
TREATMENT
• Symptomatic Treatment
TREATMENT
• Symptomatic Treatment
TREATMENT

• Treatment of complications
• Respiratory complications

Respiratory muscle weakness is an in Assessment of respiratory insufficiency

dependent predictor of quality of life. includes history, physical examination,
and respiratory failure is the most early morning arterial blood gas, and
common cause of death in ALS patients. overnight pulse oximetry.
TREATMENT

There are several types of

ventilatory aids. These are
broadly classified in terms of
invasive versus noninvasive.

As its name suggests, invasive Non- invasive ventilatory aids can be divided
techniques require an endotracheal into two groups, negative or positive
tube or more commonly a pressure ventilators. Negative pressure is
tracheostomy. For patients in exerted to the chest or abdominal wall
advanced respiratory failure (ie, no mechanically to assist inspiration. Positive
respiratory muscle function), pressure devices can be set to deliver
invasive ventilators can assume variable inspiratory and expiratory
complete control of ventilation. pressures, triggered by spontaneous effort.
TREATMENT

• Management of Dysphagia

A percutaneous endoscopic gastrostomy

Management of Dysphagia includes
(PEG) placement is indicated for those
modification of food and fluid
who have symptomatic dysphagia or
consistency, postural advice (e.g. chin
significant weight loss. Patients and their
tuck: flexing the neck forward on
families should be suitably counseled
swallowing to protect the airway), and
regarding the benefits and risks of the
parenteral feeding.
procedure.
PROGNOSIS

• Amyotrophic lateral sclerosis (ALS): Average life expectancy is

between two to five years from onset of symptoms.
• Progressive bulbar palsy (PBP): Average life expectancy is
between six months to three years from onset of symptoms.
• Progressive muscular atrophy (PMA): Average life expectancy is
usually more than five years.
• Primary lateral sclerosis (PLS): Average life expectancy may be
more than 10 years.

(www.mndassociation.org)
BIBLIOGRAPHY
• Takei, Hidehiro. 2014. Pathology of Motor Neuron Disorders. htpps://emedicine.medscape.com/article/2111360-
overview. Diakses 20 Juli 2018.
• Leigh P.N. (1991). Amyotrophic lateral sclerosis and other motor neuron disorders. Curr Opin Neurol
Neurosurg;4:586-96.
• Murros K. &, Fogelholm R. (1983). Amyotrophic lateral sclerosis in Middle-Finland: an epidemiological study. Acta
Neurol Scand;67:41-7.
• Fong K.Y., Yu Y.L., Chan Y.W., et al. (1996). Motor neuron disease in Hong Kong Chinese:epidemiology and clinical
picture. Neuroepidemiology;15:239-45.
• Radhakrishnan K., Ashok P.P., Sridharan R., Mousa M.E. (1986). Descriptive epidemiology of motor neuron disease in
Benghazi, Libya. Neuroepidemiology;5:47-54.
• Logroscino G., Traynor B.J., Hardiman O., et al. (2008). Descriptive epidemiology of amyotrophic lateral sclerosis: new
evidence and unsolved issues. J Neurol Neurosurg Psychiatry;79:6-11.
• El Thallawy, Hamdy.2013. Motor Neuron disease. https://pdfs.semanticscholar.org. Diakses 21 Juli 2018.
• Baumer, Dirk., et al. 2014.Advances in Motor Neuron Disease. Journal of the Royal Society of Medicine; 107(1) 14–21
• Lundoph, Albert., Et al. 2015. A revision of the El Escorial criteria. Amyotrophic Lateral Sclerosis and Frontotemporal
Degeneration, 2015; Early Online: 1–2
• www.mndassociation.org . Diakses 22 Juli 2018