Diagnostics

Physical examination (including testing reflexes, Babinski sign, etc.) [1][11]

Electromyography [13]

• Denervation: fibrillations, positive sharp waves, and large amplitudes

• Fasciculations

Nerve conduction studies: usually normal

Laboratory studies

• Increased creatine kinase

• Further testing of blood, urine, and CSF to exclude other causes (e.g., myasthenia gravis)

Neuroimaging: MRI to exclude other causes (e.g., cervical spondylosis)

Bedside swallowing test

Pulmonary function testing

A clinical assessment for swallowing abnormalities that involves the examination of the anatomy, function, and reflexes of the mouth, tongue, and mandible along with a trial of food and liquid

The test is considered positive if the patient is unable to drink continuously, coughs up after the swallowing attempt, and/or has a wet, gargling, or hoarse vocal quality.

Informs decisions on dietary modification (e.g., pureed food, thickened liquids, nasogastric tube, percutaneous endoscopic gastrostomy) and further investigations

If the test is positive, a formal swallowing study, such as a videofluoroscopic swallowing examination, should be performed to confirm the diagnosis.

Should be performed in all patients with ALS to screen for dysphagia.

Also performed in other neurological conditions that manifest with dysphagia, such as Parkinson disease, acute stroke, and Guillain-Barré syndrome.

Spirometry: signs of restrictive lung disease

DLCO: normal

Respiratory muscle function testing: low maximal inspiratory pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure

Macroscopic features [14]

• Atrophy of the precentral gyrus

• Thinning of ventral spinal roots

• Sclerosis and pallor of the corticospinal tract

• Muscle atrophy

Microscopic features [15]

• Death of upper and lower motor neurons

• Inclusion bodies in affected neurons, e.g.:

  • Lipofuscin

  • Bunina bodies

  • Ubiquitin-positive aggregates (associated with the protein TDP-43, which is also found in frontotemporal dementia)

• Neuroinflammation (e.g., proliferation of astroglia and microglia)

• Denervation, reinnervation, and atrophy of muscle fibers

Multifocal motor neuropathy (MMN)

• Slowly progressing asymmetrical weakness, esp. in the muscles of the distal extremities

• Muscle atrophy is rare

• EMG can reveal conduction blocks

• Highly elevated anti-GM1-ganglioside antibody titers

Myasthenia gravis

• Weakness improves with acetylcholinesterase inhibitors

• No UMN or LMN signs

Lambert-Eaton myasthenic syndrome

• Proximal muscle weakness that improves with repetitive stimulation (Lambert sign)

• Symptoms of autonomic dysfunction (e.g., dry mouth)

• Anti-VGCC antibodies

Cervical spondylosis

• Sensory symptoms

• LMN confined to affected level of spinal compression

• MRI shows spinal cord compression

Thyrotoxicosis

• Myopathy, fine tremor, and hyperreflexia resolve with treatment of hyperthyroidism

Poliomyelitis

• Asymmetric flaccid paralysis

• Poliovirus RNA in CSF