Motor neuron diseases are a group of neurodegenerative disorders that affect motor neurons in the brain and spinal cord. The presentation and progression of symptoms varies depending on whether upper motor neurons, lower motor neurons, or both are affected. Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron disease in adults and causes progressive weakness and atrophy as motor neurons degenerate. While there is no cure for motor neuron diseases, treatment focuses on managing symptoms and maximizing quality of life.

1. Presented By: Major Rehana
CMH BWP

2. INTRODUCTION:
⚫Motor neuron diseases are a group of
neurodegenerative disorders that affects the nerves
in the spine and brain to progressively lose its
function.
⚫They are a rare but serious and incurable
form of progressive neurodegeneration.
⚫It is a condition that selectively affects the motor
system, the cells which control voluntary muscles of
the body.

3. CAUSES:
⚫ The exact causes are unclear.
⚫ Some MNDs are inherited, but the causes of most MNDs are not known.
⚫ About 5% of people with motor neurone disease have a close family
relative with the condition or a related condition known as fronto
temporal dementia.
This is called familial motor neurone disease which can be hereditary
or linked to a problem with genes that can cause problems at a younger
age.
⚫ In sporadic or non inherited MNDs,
⚫ environmental,
⚫ toxic,
⚫ viral, or
⚫ genetic factors likely play a role.

4. MOTOR
NEURON
DISORDERS
UMN
Disorders UMN & LMN
Disorders
LMN
Disorders
Neurodegenerative
Disorder(Primary lateral
Sclerosis)
Toxins(Neurolathyrism)
Infections(HIV-1/2 asso.
Myelopathy)
Amyotrophic Lateral
Sclerosis
• Sporadic ALS
• Familial ALS
Neurodegenerative(Prog
Mus Atrophy;Benign focal
amyotrophy/brachial
monomelicamyotrophy)
Infections(Polio;Post
Polio;Subacute motor
neuropathyof
lymphoproliferativediseases)
Inherited(SMA;Kennedy
disease;Hexaminidase
deficiency)
Post radiation

6. ⚫Upper motor neurons (UMN) are responsible for
conveying impulses forvoluntary motoractivity
⚫UMN send fibers to the LMN, and thatexertdirector
indirect supranuclearcontrol overthe LMN.
⚫Lowermotor neurons (LMN) directly innervate the
skeletal muscle

8. 1.primary lateral sclerosis
⚫ Sporadic
⚫ No fasciculations
⚫ Nodenervation
⚫ Selective l oss of pyramidal cells
2.familial spasticparaplegia
⚫ AD
⚫ Respiratory function spared

9. ⚫ The LMNs -Located in the brainstemand spinal cord
⚫ The spinal LMNs are also known as anterior horn cell. The
neuronsareclustered in nuclei, forming longitudinal columns.
⚫ Dorsal anterior horncells -Innervatedistal muscles,
⚫ Ventral located cells- Proximal muscles,
⚫ Medially located neurons- Truncal and axial muscles.
⚫ Markedlyenlarged lateral partsof thecervical and lumbar (lower
thoracic) anterior horns innervatearm, hand, and leg muscles.
⚫ Largespinal cord LMNs arecalled alpha neurons.

10. LOWER MOTOR NEURON
Spinalcord ventral horn (Cervical spinal cord cross section)

11. 1. KENNEDY DISEASE—X LINKED SPINOBULBAR
MUSCLE ATROPHY
⚫ Males
⚫ Androgen receptor insensitivity
⚫ Gynaecomastia
⚫ Absenceof pyramidal tract signs
⚫ Sensory symptomspresent
⚫ CAG

12. 2.TAY SACHS—hexosaminidase
⚫ Cerebellaratrophy
⚫ Absentspasticity
⚫ Dysarthria
3.SMA-5q
⚫ Floppy infant
⚫ Infantile—werding hoffmandisease
4.MMNCB—
⚫ Improved on immunoglobulins,chemotherapy.

13. • Loss of Dexterity
• Loss of muscle strength (mild weakness)
• Spasticity
• Pathological Hyperreflexia
• Pathological Reflexes (Babinski, Hoffman sign, loss of
Abdominal reflexes)
• Increased reflexes in an atrophied limb(Probable UMN
sign)
• Pseudobulbar palsy (emotional lability, brisk jaw jerk,
hypeactive gag, forced yawning, snout reflex, suck
reflex, slow tongue movements, spastic dysarthria)
SIGNS & SYMPTOMS OF UMN
INVOLVEMENT

14. SIGNS & SYMPTOMS OF LMN
INVOLVEMENT
• Loss of muscle strength (moderate to severe
weakness)
• Muscle atrophy
• Hyporeflexia
• Muscle hypotonicity or flaccidity
• Fasciculations
• Muscle cramps

16. TYPES OF MND:
⚫MNDs are classified according to whether they
are inherited or sporadic(i.e-anyone can get it),
and to whether degeneration affects upper
motor neurons, lower motor neurons, or both.
⚫In adults, the most common MND is
Amyotrophic Lateral Sclerosis (ALS).

17. JeanMartin Charcot
⚫Named by Jean Martin Charcot in 19th century
⚫Also known as Lou Gehrig’s diseaseafterthe famous baseball
playerdiagnosed of ALS in 1930.
⚫Degeneration of the motor neuron(UMN & LMN) in motor
cortex,brainstem & spinal cord.
⚫Amyotrophy-Atrophyof muscle fibres consequentof
denervation due toanterior horn cell degeneration
⚫Lateral sclerosis-Sclerosis of the anterior and lateral
corticospinal tractswhich are replaced by progressivegliosis.

19. ⚫ Undetermined aetiology.
⚫ Complex genetic-environmental interaction for neuronal degenration.
⚫ 90-95% aresporadic.
⚫ Proposed hypothesis of degeneration isviral infection,immune
activation & hormonal dysfunctions.
⚫ Sporadic ALS with predominantlyautosomal dominant inheritance
⚫ Molecularpathway proposed aredue toexcitotoxicity,oxidative
stress,mitochondrial dysfunction,impaired axonal
transport,neurafilamentaggregation.
⚫ Geneticsusceptibility include APOE,SMN,peripherin,VEGF,paraoxonase
genealteration

20. ⚫ Western Pacific ALS(ALS parkinsonism dementia complex)-
Exposure to toxin β-N-methylamino-l-alanine, which is present in
seeds of theCycas circinalis in people of Chamorro natives of
Guam & Kii Peninsula of Japan.
⚫ Familial ALS(FALS)-(Type 1-10)(Type 2 & 5 have AR,rest have AD
inheritance)
i) Cu/Zn superoxidedismutase 1 (SOD1) in 20% of FALS
cases(autosomal recessive inheritance)
ii) Expansions of a GGGGCC hexanucleotide repeat in a
noncoding region of chromosome 9 is present in 37% to 46% of
FALS and 6% to 20% of sporadicALS of European descent
iii) Mutations in two RNA binding proteins, TAR DNA-binding
protein-43 (TDP-43) and fused in sarcoma (FUS)

21. ⚫ 2/3rd -Typical/Spinal form of ALS with focal motorweakness
of distal or proximal upperor lower limbs. Spread of weaknes to
contiguous muscles in thesame region beforeanotherregion is
involved.
⚫ Pseudoneuriticpattern-Involvementof muscles in the
apparentdistribution of a peripheral nerve
⚫ Monomelic-Involvementof one limb
⚫ Pseudopolyneuritic-Weakness in the both distal lower limbs
⚫ Mill’s Hemiplegicvariant-Weakness restricted toone half of
the body
⚫ Bulbar/pseudobulbar palsy

22. ⚫ 1-2% -Weakness of respiratorygroupof muscles
⚫ 10% - Bilateral upper limbweakness and wasting, flail arm of
flail person in barrel syndrome.
⚫ Head drop
⚫ Fasiculations-(Not the initial presenting symptom butalmost
seen in all patients at presentation)
⚫ Cramps-thighs,abdomen,back oreven tongue
⚫ Non motorsymptoms-Sleepdisturbance, Subtle cognitive
Dysfunctionand mood changes.
⚫Rarely involved: Bladder; bowels; Autonomic; Extraocular
movements; Sensory

23. ⚫ Morecommon in older females: 50% with bulbar
presentation
⚫ Bulbaronset in 20% to 30% of all ALS cases
⚫ Features
⚫ Dysarthria
⚫Speech rate: Slow
⚫Voice quality: Reduced
⚫ Dysphagia
•Coticobulbar tracts involvement
•Spasticdysarthria,dysphonia,dysphagia
•Emotional lability(forced crying or laughter)
•Brisk jaw jerk
•Hyperactivegag ref lex

24. TYPES
⚫ALS, or Lou Gehrig's disease, is the most common
type, affects both the UMN and LMN. It can affect the
muscles of the arms, legs, mouth, and respiratory
system. Mean survival time is 3 to 5 years, but some
people live 10 years or more beyond diagnosis with
supportive care.
⚫Progressive bulbar palsy (PBP) involves the brain
stem(LMN). People with ALS often have PBP too.
The condition causes frequent choking spells,
difficulty speaking, eating, and swallowing.

25. ⚫Diagnosisof exclusion
⚫Account for 2-4% of ALS
⚫Absenceof LMN Invovement
⚫Presentation in early 50’s
⚫Slowlyevolving spastic paresis after involving upper
limbs.
⚫Median diseaseduration:19yrs
⚫Fasiculation,cramps,bladderdysfunction,cognitive
deficits & abnormal voluntaryeye movement
⚫Striking loss of Betz cells in layer 5 of frontal and
prefrontal cortex with laminargliosis of layers 3 & 5 and
degeneration corticospinal tract

26. TYPES
⚫Pseudobulbar Palsy: This is similar to progressive bulbar
palsy. It affects motor neurons that control the ability to
talk, chew, and swallow. Pseudobulbar palsy causes people
to laugh or cry with no control.
⚫Progressive muscular atrophy (PMA): It only affects
the LMN in the spinal cord. Affects slowly but
progressively causes muscle wasting, especially in the
arms, legs, and mouth. It may be a variation ofALS.
⚫Primary lateral sclerosis (PLS): It is a disease of UMN. It
is the rare form of MND that advances more slowly than
ALS. It is not fatal, but it can affect the quality of life. In
children, it is known as juvenile primary lateral sclerosis.

27. TYPES
⚫Spinal muscular atrophy (SMA) is an inherited MND that
affects children. There are three types, all caused by an
abnormal gene known as SMA1(This gene makes a protein
that protects the motor neurons. Without it, they die.). It
tends to affect the trunk, legs, and arms. Long-term outlook
varies according to type.
⚫The different types of MND share similar symptoms,
but they progress at different speeds and vary in
severity.

28. DIAGNOSIS
• No biological marker has been identified yet.
• Series of clinical and neurological exams.
• MRI
• Myelogram of cervical spine (an x-ray analysis that allows the
detection of lesions in selected area of the spinal cord)
• Muscle and/or nerve biopsy
• Electromyography (EMG) and nerve conduction velocity (NCV)
to measure muscle response to nervous stimulation.

29. ⚫After tests, a doctor will normally monitor the patient
for some time before confirming that they have MND.
⚫Criteria known as El Escorial criteria can help a doctor
check for distinctive neurological signs, that may aid in
the diagnosis ofALS.
⚫These include:
⚫muscle shrinking, weakness or twitching
⚫muscle stiffness or abnormal reflexes
⚫symptoms spreading into new muscle groups
⚫having no other factors that explain the symptoms

31. EL ESCORIAL DIAGNOSTIC CRITERIA

32. ⦿ Other Motor Neuron Diseases
◾ Primary lateral sclerosis (UMN only)
◾ Progressive muscular atrophy (LMN
only)
◾ Progressive bulbar palsy
⦿ Structural lesions
◾ cervical spondylosis
◾ parasaggital/foramen magnum
tumor
◾ spinal cord AV malformation
⦿ Neuropathies
◾ CIDP
⦿ Myopathies
◾ PM, inclusion body myositis
⦿ NM Junction
◾ Myasthenia gravis
⦿ NEURODEGENERATIVE DISEASES
◾ Parkinson’s, Progressive Supranuclear
Palsy, Multiple sclerosis.
⦿ Malignancy
◾ Primary/metastasis to CNS
◾ Motor neuron syndromes with MM,
Lymphoma, lung, breast.
⦿ Toxic Exposure
◾ alcohol, heavy metals.
⦿ Endocrine
 hyperthyroidism
 hyperparathyroidism.
⦿ Infectious
◾ HIV
, CMV
Differential Diagnosis

33. TREATMENT:
⚫There is no cure for MND, so treatments focus
on relieving the symptoms, slowing the
progression and maximizing patient
independence and comfort.
⚫This can include the use of breathing,
feeding, mobility and communication
appliances and devices.
⚫Rehabilitation therapy may include physical,
occupational and speech therapy.

34. MEDICAL MANAGEMENT:
⚫ Two drugs are currently approved by the U.S. Food and Drug
Administration (FDA) forALS.
⚫ Riluzole or Rilutek lowers the amount of glutamate in the body.
It appears most effective in the early stages ofALS and in older
individuals. It has been given to improve survival.
⚫ In early 2017, the drug Radicava (Endaravone) was approved
by the FDAfor the treatment ofALS.
⚫ How it works is not well understood, but it may delay disease
progression by working against tissue damage.
⚫ Scientists are currently exploring a possible role for stem cells in
the treatment ofALS.

35. ⚫Muscle cramps and stiffness can be treated with
physical therapy and medications, such botulinum toxin
(BTA) injections. BTAblocks the signals from the brain
to the stiff muscles for about 3 months.
⚫Scopolamine, a drug for motion sickness, may help
control symptoms of drooling. It is worn as a patch
behind the ear.
⚫Antidepressants, called serotonin reuptake inhibitors
(SSRIs), may help with episodes of uncontrollable
laughter or crying, known as emotional lability.
⚫Advice from a speech and language therapist.
⚫Advice from a dietitian about diet and eating.

36. PROGNOSIS:
⚫Prognosis varies depending on the type of MND
and the age of onset.
⚫Some MNDs, such as PLS are not fatal and
progress slowly.
⚫People with SMAmay appear to be stable for
long periods, but improvement should not be
expected.
⚫Some MNDs, such asALS and some forms of
SMA, are fatal.