Motor neuron diseaseMND:ALS

Dr. Mohammad Shaikhani.

Lou Gehrig’s Disease

• A well-known baseball player.

• He was diagnosed with ALS.

• Within a year, he could not walk or talk.

• He died in 1941.

MND (ALS): • A progressive disorder of unknown cause.• There is degeneration of motor neurons in the spinal

cord,cranial nerve nuclei& pyramidal neurons in the motor cortex.

• 5% of cases are familial, AD, the genetic defect on ch 21, the enzyme involved superoxide dismutase (SOD1).

• For the remaining 95% unknown cause, ? viral infection, trauma, exposure to toxins , electric shock.

MND (ALS): • A relentlessly progressive disorder with incidence of 2/ 100,000 • Most cases are acquired or sporadic, 5- 10% inherited• 20% with inherited ALS have a mutation in the superoxide dismutase gene( important mediator

in free-radical pathways) lead to excessive free-radical damage to anterior horn cells. • Patients report progressive painless weakness, atrophy, fasciculations beginning in an arm or leg. • Patients do not have sensory loss, pain, or impairment in bowel &bladder function. • Combinations of LMN signs of atrophy& fasciculations&UMN signs,as hyperreflexia& extensor

plantars, are typically seen. • 20% have bulbar-onset ALS, characterized by slurred speech, difficulty swallowing&emotional

lability. • As ALS progresses, patients develop weight loss& resp failure. • The presence of cognitive impairment, specifically frontotemporal dementia, is being increasingly

recognized in some patients.

MND (ALS): • Neurologic exam: limb weakness, fasciculations, atrophy, brisk deep tendon

reflexes&extensor plantar responses.• Signs of bulbar impairment (such as slurred speech), tongue atrophy&

fasciculations may also be evident. • MRI of the brain/spinal cord should be performed to exclude a structural lesion. • EMG is essential to rule out other disorders &to establish the extent / severity of

denervation. • Pulmonary function tests&overnight pulse oximetry studies can establish the

presence of respiratory insufficiency. • Patients with bulbar signs or symptoms require evaluation of swallowing

function.

MND (ALS):Management • Symptom based& referral to a multidisciplinary ALS clinic for

ongoing care / support is beneficial.

MND (ALS): Management • Interventions that improve survival:• 1.Riluzole, a glutamate antagonist, is the only medication approved & can slow

the decline of muscle weakness& prolong survival by a median of 83 days. • 2.Noninvasive positive-pressure ventilation(NIV) with bilevel positive airway

pressure has also been shown to prolong survival & improve quality of life. • Indications for ventilatory support:• Symptoms of nocturnal hypoventilation• A forced vital capacity < 50%• Nocturnal oxygen saturation < 90% for > 1 minute• A maximal inspiratory pressure of < 60 cm H2O• A maximal expiratory pressure of < 30 cm H2O.

MND (ALS): symptomatic trt • 1.Placement of a PEG improve the quality of life, when patients

experience a 10% or greater weight loss, require 30 minutes or more to finish a meal, or have episodes of coughing&choking when eating.

• 2.Excessive salivation can be treated symptomatically with: • Anticholinergic agents, as glycopyrrolate,amitriptyline& benztropine. • Injection of botulinum toxin into the parotid or submandibular glands if

above fail. • 3.Excessive emotional lability can be treated with either TAD or SSRI. • 4. Speech: augmentative & alternative communication devices can help

preserve communication when speech becomes unintelligible.

MND (ALS):

Clinical features: • A combination of lower &upper motor neuron signs without sensory

involvement. • The presence of brisk reflexes in wasted fasciculating limb muscles is typical. • In many patients the clinical features are highly suggestive but alternative

diagnoses need to be carefully excluded specially potentially treatable disorders as;

• Diabetic amyotrophy.• Spinal disorders .• Multifocal motor neuronopathy. • CSF exam is usually normal, though a slight elevation in protein may be

found.

Clinical features:

Usually after 50 years Very uncommon before 30 years Affects males > females

Onset

Clinical features: Symptoms

Limb muscle weakness, cramps, occasionally fasciculation Disturbance of speech/swallowing (dysarthria/dysphagia)

Clinical features: Signs

Signs Signs

Wasting and fasciculation of muscles Weakness of muscles of limbs, tongue, face & palate Pyramidal signs: spasticity, inc tendon reflexes, extensor plantar. External ocular muscles intact. Sphincters remain intact. No objective sensory deficit. No intellectual impairment in most cases until late .

Clinical features: course

Signs Signs

Symptoms often begin focally in one part & spread gradually but eventually become widespread

Clinical features: involvement patterns 1.Progressive muscular atrophy

Predominantly spinal motor neurons affected

Weakness / wasting of distal limb muscles at first

Fasciculation in muscles

Tendon reflexes may be absent Signs Signs

Clinical features: involvement patterns

Signs Signs

2.Progressive bulbar palsy

Early involvement of tongue, palate and pharyngeal muscles Dysarthria/dysphagia Wasting / fasciculation of tongue +/- pyramidal signs.

Clinical features: involvement patterns

Signs Signs

3.Amyotrophic lateral sclerosis

Combination of distal & proximal muscle-wasting & weakness, fasciculation Spasticity, exaggerated reflexes, extensor plantars Bulbar & pseudobulbar palsy follow eventually Pyramidal tract features may predominate

DD:

Signs Signs

Management: • The glutamate antagonist, riluzole, shown to have a small effect in prolonging life expectancy

by about 2 month. • It is not clear at which stage of the illness this prolongation occurs, so may not be particularly

helpful. • Other agents such as nerve growth factor show promise. • Psychological / physical support, with help from occupational / speech therapists /

physiotherapists, are essential to maintain the patient's quality of life. • Mechanical aids such as splints, walking aids, wheelchairs / communication devices all help to

reduce handicap. • Feeding by percutaneous gastrostomy may be necessary if bulbar palsy is marked. • Sometimes non-invasive ventilatory support may help distress from weak respiratory muscles

although maintenance ventilation is usually not requested. • Relief of distress in the terminal stages usually requires the use of opiates & sedative drugs.

Management: • The only drug currently available is riluzole (2-amino-6-

[trifluoromethoxy]benzothiazole).• Riluzole blocks glutamic acid release, may slow disease

progression by disrupting glutamate-mediated neurotoxicity. • Administered at 50 mg twice a day,• Riluzole is generally well-tolerated,but may cause nausea ,

general asthenia& methaemoglobinura in overdose.

Management:Future • 1.long-term ceftriaxone slowed the course of disease in a mouse

model, if given in high doses at the onset of the disease, preserved grip strength, slowed weight loss, & increased the overall duration of survival from 122 - 132 days &the mechanism is by modulating glutamate transport.

• 2.Gene therapy • 3. RNA silencing

Prognosis: • It 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 & those with early bulbar symptoms tend to show a more rapid course.

• Death is usually from respiratory infection / failure& the complications of immobility.

TYPES OF SPINAL MUSCULAR ATROPHY

Type Onset Inheritance Features Prognosis

Werdnig-Hoffmann

Infancy Autosomal recessive

Severe muscle-wasting/weakness Poor

Kugelberg-Welander

Childhood, adolescence

Autosomal recessive

Proximal weakness and wasting, EMG shows denervation

Slowly progressive disability

Distal forms Early adult life Autosomal dominant

Distal weakness and wasting of hands and feet

Good, seldom disabling

Bulbospinal Adult life, males only

X-linked Facial / bulbar weakness, proximal limb weakness, gynaecomastia

Good