ALS

What is amyotrophic lateral sclerosis (ALS)?

A progressive, fatal neurodegenerative disease affecting upper and lower motor neurons.

Which structures are affected by ALS?

Motor cortex UMNs, spinal anterior horn LMNs, and corticobulbar pathways/cranial nerve motor nuclei involved in speech and swallowing.

What is the most common cause of death in ALS?

Respiratory failure due to weakness of respiratory muscles.

What incidence, prevalence, and peak-incidence age are quoted in the file?

Incidence: 1.5–2 per 100,000/year; prevalence: 4–6 per 100,000; peak incidence: the 70s.

What survival figures are quoted in the file?

Typical survival is 2–4 years from first symptom; approximately 10% survive over 10 years.

How common are frontotemporal dementia and milder cognitive/behavioral changes in ALS?

FTD occurs in approximately 15%; mild cognitive/behavioral changes may occur in up to 50%.

How do sporadic and familial ALS differ in frequency, onset, and sex distribution?

Sporadic: about 90%, onset 60–65 years, male:female 1.5:1; familial: about 10%, onset 50–55 years, men and women equally affected.

Which possible risk factors and associations are listed for ALS?

Smoking is the most consistent possible risk factor; trauma, intense physical activity, certain occupations, and military service are associations rather than proven causes.

What is the C9orf72 mutation associated with ALS?

A GGGGCC repeat expansion, linked strongly to FTD; quoted in about 40% of familial and 5–10% of sporadic ALS.

What is the importance of SOD1 in ALS?

It lies on chromosome 21, accounts for about 15–20% of familial cases in the file, and is the target of tofersen.

What combination of examination findings is a hallmark of ALS?

UMN and LMN signs in the same limb, such as a wasted, twitching arm with brisk reflexes.

Which UMN signs are listed in ALS?

Hyperreflexia, spasticity, brisk jaw jerk, positive Babinski, and positive Hoffmann signs.

Which LMN signs are listed in ALS?

Fasciculations, muscle wasting, asymmetric weakness, and muscle cramps, often at night.

Which functions are usually spared in ALS?

Sensation, eye movements, and bladder and bowel control.

How do bulbar-onset and limb-onset ALS differ in frequency and prognosis?

Bulbar onset: 25–30%, generally shorter survival; limb onset: about 70%, generally longer survival.

What are the main presenting features of bulbar-onset ALS?

Dysarthria and dysphagia, with tongue atrophy and fasciculations at rest.

What are typical presenting features and progression of limb-onset ALS?

Asymmetric hand/foot weakness, difficulty buttoning clothes, or foot drop; spread to other limbs over months, with bulbar involvement later.

What additional bulbar signs and emotional changes can occur in ALS?

Weak neck flexion, weak lip closure, poor palate elevation, and pseudobulbar affect with sudden laughing or crying.

How is ALS diagnosed, and can a blood test confirm it?

It is a clinical diagnosis supported by EMG; no blood test confirms ALS.

What diagnostic requirements are listed in the file?

Progressive motor weakness; UMN plus LMN signs in at least one region, or LMN signs in at least two regions; and exclusion of other causes.

What EMG findings support ALS?

Widespread denervation, fibrillations, fasciculations, and chronic reinnervation, including in muscles that still appear strong.

What regional and nerve-conduction pattern supports ALS?

Motor involvement across bulbar, cervical, thoracic, and lumbar regions, with normal sensory nerves and no conduction block.

Which findings favor cervical myelopathy or syringomyelia over ALS?

Cervical myelopathy: neck pain, sensory loss, bladder symptoms, an MRI lesion, and absent bulbar signs; syringomyelia: cape-like pain/temperature loss.

How do inclusion body myositis and benign cramp–fasciculation syndrome differ from ALS?

Inclusion body myositis: finger-flexor/quadriceps involvement without UMN signs, assessed by biopsy; benign fasciculations: twitching without progressive weakness, wasting, or UMN signs.

What findings suggest multifocal motor neuropathy rather than ALS?

Pure LMN signs in a nerve distribution, conduction block, and anti-GM1 antibodies; it is treatable with IVIG.

What is Kennedy disease, and how is it inherited?

Spinal and bulbar muscular atrophy (SBMA), an X-linked recessive disorder affecting men.

Which features distinguish Kennedy disease from ALS?

Gynecomastia/testicular atrophy, mild sensory neuropathy, slow progression over years to decades, usually absent UMN signs, and frequently elevated CK.

Which genetic test confirms Kennedy disease?

Detection of a CAG repeat expansion in the androgen receptor gene.

How does riluzole act, and what benefit is quoted in the file?

It reduces glutamate release and blocks sodium channels; the file quotes a survival extension of approximately 2–3 months and describes it as standard care for most patients.

How does edaravone act, and which patients are described as candidates?

It scavenges free radicals and reduces oxidative stress; it may slow functional decline in selected early-stage patients, with evidence/approval varying.

How does tofersen work, and which ALS subgroup is targeted?

An intrathecal antisense oligonucleotide that reduces SOD1 protein and neurofilament levels, targeting patients with SOD1-associated ALS.

What is the role of multidisciplinary care and non-invasive ventilation in ALS?

Multidisciplinary clinics improve survival and quality of life; NIV prolongs survival.

Which NIV indications and advanced respiratory planning points are listed?

Orthopnea, morning headache, or FVC below 50%; discuss tracheostomy early according to patient preferences.

When should PEG feeding be considered, and what timing does the file recommend?

Consider it when swallowing fails or weight decreases; the file recommends placement while FVC remains above 50%, to support nutrition and weight maintenance.

What rehabilitation, communication, symptom-control, and palliative measures are listed?

Physiotherapy, splints, and mobility aids; speech therapy and eye-gaze devices; treatment of drooling, spasticity, cramps, and pseudobulbar affect; early palliative planning.