AMYOTROPIC LATERAL

SCLEROSIS
Dr. Akshata Nadgir
 Also called as Lou Gehrig disease
 It is a relentless, degenerative, terminal disease affecting both upper and lower motor
neurons.
 Massive loss of anterior horn cells of the spinal cord and the motor cranial nerve nuclei
in the lower brain stem results in muscle atrophy and weakness (amyotrophy).
 Demyelination and gliosis of the corticospinal tracts and corticobulbar tracts caused by
degeneration of the Betz cells in the motor cortex result in upper motor neuron
symptoms (lateral sclerosis).
 Men are affected nearly twice as often as women. Most patients are older than age 45
years at the onset of symptoms, and the incidence increases with each decade of life

INTRODUCTION
 90% of cases are sporadic without known genetic component
 In approximately 10 percent of cases the disease is familial, being inherited as an autosomal dominant trait with age-
dependent penetrance..
 TDP-43 proteinopathy
 5% to 10% of the cases seem to have a complex genetic basis coded on ALS1 through ALS8 and other mutations that are
associated with frontal lobe dementias
 Twenty percent of genetic causes of ALS are thought to be related to mendelian mutations in the superoxide dismutase–1
(SOD1) gene (ALS1).
 Vascular endothelial growth factors
 Toxicity leading to motor neuron death
 Oxidative stress and mitochondrial dysfunction related to microglial inflammation
 Environmental factors.

CAUSES
 Approximately 70% of patients and tend to be higher in patients with limb onset ALS
rather than bulbar onset
 Genetic testing to identify the mutations in the Cu, Zn SOD1 gene is available when a
family history of ALS is present.
 Biochemical markers in the blood and cerebrospinal fluid, are used to exclude other
neurological diseases.
 Electromyography(EMG) and nerve conduction
 Neuroimaging studies

DIAGNOSIS
 Progressive degeneration and loss of motor neurons in the spinal cord, brainstem, and
motor cortex
 UMNs in the cortex are affected, as are the corticospinal tracts. Brainstem nuclei for
cranial nerves V (trigeminal), VII (facial), IX (glossopharyngeal), X (vagus), and XII
(hypoglossal) and anterior horn cells in the spinal cord are also involved.
 Brainstem nuclei for cranial nerves controlling external ocular muscles (III: oculomotor
IV: trochlear, and VI: abducens) are usually spared
 Degeneration of Clarke’s neurons and of the spinocerebellar tracts has also been reported.
 Degeneration of the spinocerebellar tracts is a well recognized pathological feature of
FALS and has been described in sporadic ALS, although it is rare. Posterior column
degeneration is more common in FALS, but is rare in sporadic ALS.

PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
 The World Federation of Neurology (WFN) has developed suggested diagnostic criteria (suspected,
possible, probable, and definite) for patients with ALS. Essentially, a patient with “definite” ALS must
show concomitant upper motor neuron and lower motor neuron signs in three spinal regions or in
two spinal regions with bulbar signs.
 Either upper or lower motor signs must also be evident in other regions of the body.
 Exclusionary criteria are oculomotor nerve pathway abnormalities (the oculomotor nerve is spared in
ALS), significant movement disorder patterns, sphincter control problems, the presence of sensory and
autonomic nervous system (ANS) dysfunction, and cognitive deterioration.
 Absence of sensory involvement
 Cognitive deficits- manifested as a decrement in executive skills such as planning and organization and
language problems

CLINICAL MANIFESTATION
 The earliest clinical markers heralding ALS are
fasciculations (especially unequivocal fasciculation in
the tongue), muscle cramps, fatigue, weakness, and
atrophy
 A typical, but not absolute, pattern of motor progression
is early distal involvement followed by proximal limb
involvement. In some cases bulbar symptoms herald the
onset of ALS, but bulbar symptoms more commonly
occur later in the disease. Flexor muscles tend to be
weaker than extensor muscles
 80% or more of patients show early clinical evidence of
pyramidal tract dysfunction (e.g., hyperreflexia in the
presence of weakness and atrophy, spasticity, and
Babinski and Hoffmann reflexes).
 Onset is varied. Lower-extremity onset is slightly more
common than upper-extremity onset, which is more
common than bulbar onset.
 Bulbar symptoms are presaged by tongue fasciculations and weakness, facial and
palatal weakness, and swallowing difficulties, which result in dysphagia and dysarthria.
 Pseudobulbar palsy is sometimes present in ALS, manifested by spontaneous laughing
or crying unrelated to the situation.
ALS SEVERITY SCALE FOR RAPID FUNCTIONAL ASSESSMENT OF DISEASE
STAGE. THEIR 10-POINT ORDINAL SCALE ALLOWS CLINICIANS AND
THERAPISTS TO SCORE PATIENTS IN FOUR CATEGORIES: SPEECH,
SWALLOWING, AND LOWER-EXTREMITY AND UPPER-EXTREMITY FUNCTION
 Focal, asymmetrical muscle weakness beginning in the
lower extremity (LE) or upper extremity (UE), or
weakness of the bulbar muscles.
 Initial muscle weakness usually occurs in isolated
muscles, most often distally, and is followed by
progressive weakness and activity limitations
 Individuals with bulbar onset may notice changes in their
voice, difficulty moving the tongue, or decreased ability
to move the lips or open or close the mouth
 Cervical extensor weakness is common

LMN LESION
 The diagnosis of ALS requires the presence of
 LMN signs by clinical, electrophysiological, or neuropathological examination;
 UMN signs by clinical examination;
 Progression of the disease within a region or to other regions by clinical examination or via the medical history.
 The absence of (1) electrophysiological and pathological evidence of other diseases that may explain the UMN
and LMN signs;
 (2) neuroimaging evidence of other disease processes that may explain the observed
 clinical and electrophysiological signs are also evaluated

DIAGNOSIS
 50% survival probability after the first symptom of ALS appears is slightly
greater than 3 years, unless mechanical ventilation is used to sustain breathing.
 In most patients, death occurs within 3 to 5 years after diagnosis and usually
results from respiratory failure.

DISEASE COURSE
MANAGEMENT
 DMA
 anti-cramping
 antispasticity agents,
 drying agents for sialorrhea
 Antidepressants
 Dysphagia management

MEDICAL MANAGEMENT
PHYSIOTHERAPY MANAGEMENT
 Cognition: MMS
 Psychosocial Function: he Beck’s Depression Inventory the Center of
Epidemiologic, Study Depression Scale,the Hospital Anxiety and Depression
Scale (HADS) and the State-Trait Anxiety Inventory
 Pain: VAS
 Joint integrity, Range of Motion and Muscle length: Functional ROM, active,
active-assisted, and passive range ROM, muscle length, and soft tissue flexibility
and extensibility
 Muscle Performance: MMT and MVIC
 Motor Function

ASSESSMENT
 Tones and Reflexes: MAS and Tardieu
 Cranial Nerve Integrity: V, VII, IX, X, and XII.
 Sensation
 Postural Alignment, Balance and Control: POMA, BBS, TUG and FRT
 Gait
 Respiratory function: Sniff nasal pressure, FVC, VC, MIP, PCEF
 Functional Status: FIM, The Schwab and England Activities of Daily Living
Scale
 Environmental Barriers
 Fatigue
 Others: ALSFRS-R, Appel ALS Scale (AALS), the ALS Severity Scale
(ALSSS) and the Norris Scale
 Quality of Life: Schedule for Evaluation of Individual Quality of Life— Direct
Weighting (SEIQoL-DW) and the Sickness Impact Profile (SIP) and the
Amyotrophic Lateral Sclerosis Assessment Questionnaire