MOTOR NEURON DISEASE of the neurological system

Motor Neuron Disease (MND) is a progressive neurological disorder affecting motor neurons in the brain and spinal cord, leading to muscle weakness, atrophy, and eventual paralysis. Common types include Amyotrophic Lateral Sclerosis (ALS). MND impairs movement, speech, swallowing, and breathing, often with fatal outcomes.

1. Clinical Vignette
A 62-year-old female first noted difficulty walking
over uneven ground. Progressive painless weakness
developed over the course of the next 6 months;
initially this affected the left leg more than the right,
resulting in a number of falls. By the time she was
evaluated by a neurologist, she could no longer cut
her own food or clip her own finger nails. She denied
any pain, sensory disturbance or change in her ability
to think, speak, swallow, or breathe.

2. MOTOR NEURON DISEASE
Dr K.M. Bhargav
MBBS, MD, MRCP (UK)
Diploma in Health Economics
Ex-Respiratory Registrar, RLI, UK

3. INTRODUCTION
This is a progressive disorder of unknown
cause.
There is degeneration of motor neurons in the
spinal cord and cranial nerve nuclei, and of
pyramidal neurons in the motor cortex.

4. ETIOLOGY
 Familial and AD-5%
chromosome 21, enzyme (SOD1).
Others include viral infection, trauma, exposure to
toxins and electric shock
The prevalence of the disease is about 5/100 000.

5. Sporadic Motor Neuron Diseases
Chronic
 Upper and lower motor neurons
Amyotrophic lateral sclerosis
 Predominantly upper motor neurons
Primary lateral sclerosis
 Predominantly lower motor neurons
Multifocal motor neuropathy with conduction block
Motor neuropathy with paraproteinemia or cancer
Motor-predominant peripheral neuropathies
 Other
Associated with other degenerative disorders
Secondary motor neuron disorders

6. Sporadic Motor Neuron Diseases
Acute

Poliomyelitis
 Herpes zoster
 Coxsackie virus

7. Secondary motor neuron disorders
Structural lesions
Parasagittal or foramen magnum tumors
Cervical spondylosis
Chiari malformation or syrinx
Spinal cord arteriovenous malformation
Infections
Bacterial—tetanus,
Viral—poliomyelitis, herpes zoster
Retroviral myelopathy
Intoxications, physical agents
Toxins—lead, aluminum, others
Drugs—strychnine, phenytoin
Electric shock, x-irradiation

8. Secondary motor neuron disorders
Immunologic mechanisms
Plasma cell dyscrasias
Autoimmune polyradiculoneuropathy
Motor neuropathy with conduction block
Paraneoplastic
Metabolic
Hypoglycemia
Hyperparathyroidism
Hyperthyroidism
Deficiency of folate, vitamin B12,
Malabsorption
Mitochondrial dysfunction

9. Pathology
The pathologic hallmark of motor neuron degenerative
disorders is :
death of lower motor neurons (consisting of anterior horn
cells in the spinal cord and their brainstem homologues
innervating bulbar muscles)
and upper, or corticospinal, motor neurons (originating in
layer five of the motor cortex and descending via the
pyramidal tract to synapse with lower motor neurons,
either directly or indirectly via interneurons).

10. Pathology
At its onset ALS may involve selective loss of function of only
upper or lower motor neurons,
it ultimately causes progressive loss of both categories of motor
neurons.
Other motor neuron diseases involve only particular subsets of
motor neurons.
In bulbar palsy and spinal muscular atrophy (SMA; also called
progressive muscular atrophy), the lower motor neurons of
brainstem and spinal cord, respectively, are most severely
involved.
Pseudobulbar palsy, primary lateral sclerosis (PLS), and
familial spastic paraplegia (FSP) affect only upper motor
neurons innervating the brainstem and spinal cord are involved

11. Pathology
In these diseases, the affected motor neurons undergo
shrinkage, often with accumulation of the pigmented lipid
(lipofuscin) that normally develops in these cells with
advancing age.
In ALS, the motor neuron cytoskeleton is typically affected
early in the illness.
Focal enlargements are frequent in proximal motor axons;
ultrastructurally, these “spheroids” are composed of
accumulations of neurofilaments.
Also seen is proliferation of astroglia and microglia, the
inevitable accompaniment of all degenerative processes in the
central nervous system (CNS).

12. Amyotrophic lateral sclerosis. MRI scan through the lateral ventricles of the brain reveals
abnormal high signal intensity within the corticospinal tracts (arrows). This MRI feature
represents an increase in water content in myelin tracts undergoing Wallerian
degeneration secondary to cortical motor neuronal loss

13. Pathology
The death of the peripheral motor neurons in the brainstem and
spinal cord leads to denervation and consequent atrophy of the
corresponding muscle fibers.
As denervation progresses, muscle atrophy is readily recognized in
muscle biopsies and on clinical examination. This is the basis for the
term amyotrophy.
The loss of cortical motor neurons results in thinning of the
corticospinal tracts that travel via the internal capsule and brainstem
to the lateral and anterior white matter columns of the spinal cord.
The loss of fibers in the lateral columns and resulting fibrillary gliosis
impart a particular firmness (lateral sclerosis).
A remarkable feature of the disease is the selectivity of neuronal cell
death.

14. Pathology
By light microscopy, the entire sensory apparatus, the regulatory
mechanisms for the control and coordination of movement, and the
components of the brain that are needed for cognitive processes,
remain intact.
However, immunostaining indicates that neurons bearing ubiquitin, a
marker for degeneration, are also detected in nonmotor systems.
Moreover, studies of glucose metabolism in the illness also indicate
that there is neuronal dysfunction outside of the motor system.
Within the motor system, there is some selectivity of involvement.
Thus, motor neurons required for ocular motility remain unaffected, as
do the parasympathetic neurons in the sacral spinal cord that innervate
the sphincters of the bowel and bladder.

15. Clinical Manifestations
Onset
Usually after the age of 50 years
Very uncommon before the age of 30 years
Affects males more commonly than females
Symptoms

Limb muscle weakness, cramps, occasionally
fasciculation.

Disturbance of speech/swallowing
(dysarthria/dysphagia).

16. Clinical Manifestations
Signs
Wasting and fasciculation of muscles
Weakness of muscles of limbs, tongue, face and palate
Pyramidal tract involvement causes spasticity, exaggerated
tendon reflexes, extensor plantar responses
External ocular muscles and sphincters usually remain intact
No objective sensory deficit
No intellectual impairment in most cases
Course

Symptoms often begin focally in one part and spread
gradually but relentlessly to become widespread

17. PATTERNS OF INVOLVEMENT OF
MOTOR NEURON DISEASE
Progressive muscular atrophy
Predominantly spinal motor neurons affected
Weakness and wasting of distal limb muscles at first
Fasciculation in muscles
Tendon reflexes may be absent
Progressive bulbar palsy

Early involvement of tongue, palate and pharyngeal muscles

Dysarthria/dysphagia

Wasting and fasciculation of tongue

May be pyramidal signs as well
Amyotrophic lateral sclerosis

Combination of distal and proximal muscle-wasting and weakness, fasciculation

Spasticity, exaggerated reflexes, extensor plantars

Bulbar and pseudobulbar palsy follow eventually

Pyramidal tract features may predominate

18. DIAGNOSIS
In many patients the clinical features are highly suggestive but
alternative diagnoses need to be carefully excluded.
In particular, potentially treatable disorders such as diabetic
amyotrophy, spinal disorders and multifocal motor neuronopathy
should be excluded.
Electromyography helps to confirm the presence of fasciculation and
denervation, and is particularly helpful when pyramidal features
predominate.
Sensory nerve conduction and motor conduction studies are normal but
there may be some reduction in amplitude of action potentials due to
loss of axons.
Spinal imaging and brain scanning may be necessary to exclude focal
spinal or cerebral disease.
CSF examination is usually normal, though a slight elevation in protein
concentration may be found.

19. Management
No treatment arrests the underlying pathologic
process in ALS.
The drug riluzole (100 mg/d) was approved for
ALS because it produces a modest lengthening of
survival.
Edaravone antioxidant
Phenylbutyrate and taurusodiol
Other agents such as nerve growth factor show
promise.

20. Management
Psychological and physical support,
with help from occupational and speech therapists and
physiotherapists, are essential to maintain the patient's
quality of life.
Mechanical aids such as splints, walking aids,
wheelchairs and communication devices all help to
reduce handicap.
Feeding by percutaneous gastrostomy may be
necessary if bulbar palsy is marked.
Relief of distress in the terminal stages usually
requires the use of opiates and sedative drugs.

21. Prognosis
Motor neuron disease is progressive;
The mean time from diagnosis to death is 1
year, with most patients dying within 3-5
years of the onset of symptoms.
Younger patients and those with early bulbar
symptoms tend to show a more rapid course.
Death is usually from respiratory infection and
failure, and the complications of immobility.

22. Summary

23. THANK YOU