Amyotrophic Lateral Sclerosis (ALS) Flashcards
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND), a progressive neurodegenerative disease characterised by worsening paralysis, disability and eventually death.
Amyotrophic lateral sclerosis (ALS) - When does it develop?
It tends to develop in the mid-to-late 50’s and is seen more commonly in men. Presentations can vary significantly but the onset is commonly with asymmetrical weakness of a limb. The disease is progressive, eventually affecting more muscles groups, including those involved in respiration. Death most commonly results from respiratory failure, with a median survival of 3-5 years after symptom onset.
ALS epidemiolgoy
The majority of cases, around 90%, are sporadic whilst the remaining 10% are familial. Sporadic disease occurs more commonly in men than in women (almost 2:1) though the gender balance is more even in inherited disease.
Onset is typically in the mid to late 50’s though early onset is seen in familial forms of the disease.
The … expansion is the most commonly identified mutation in patients with familial ALS.
The C9orf72 expansion is the most commonly identified mutation in patients with familial ALS.
ALS can present in a myriad of ways affecting different parts of the body with upper and/or lower motor neuron signs.
What are the most common forms of presentation?
The most common forms of presentation are asymmetrical limb onset (around 80%) followed by bulbar onset (around 20%). Rarer presentations include diaphragmatic onset and more generalised presentations.
Bulbar onset - ALS
Around a fifth of patients will present with bulbar onset with features of dysarthria and dysphagia. A change in the character of ones voice may be noted. Patients may have difficulty swallowing leading to choking or aspiration.
Cognitive symptoms in ALS
There is a strong association between ALS and frontotemporal dementia which affects around 15% of patients. All patients should be screened at presentation and at regular follow-ups for dementia.
A ‘pseudobulbar affect’ may be seen - this describes involuntary laughing and crying. Other mood changes may be seen either in conjunction with frontotemporal dementia or independent of it.
Findings depend on the site of onset, the mix of UMN and LMN signs and the stage of progression. Generally clinical signs can be divided into either UMN or LMN.
LMN - ALS
Weakness
Muscle atrophy
Hyporeflexia
Fasciculations
Muscle cramps
Dysarthria, dysphagia (tongue and pharyngeal weakness)
UMN - ALS
Hypertonia
Hyperreflexia
Spastic gait
Ankle clonus
Jaw clenching
Exaggerated jaw jerk
Dysarthria, dysphagia (due to lack of coordination and spastic dysarthria)
Natural history of ALS
The disease is relentlessly progressive, thought the rate varies between individuals. After onset, disease spreads to other muscle groups, at times following a sequential pattern. For example those with unilateral arm onset may then see the contralateral affected followed by the ipsilateral leg, contralateral leg and then bulbar muscles. A similar pattern may be seen in those with unilateral leg onset (first to the contralateral leg etc).
With time bulbar symptoms become more troublesome, with increasing swallowing difficulties impacting nutrition and risking aspiration events. Muscle weakness turns to atrophy and weight loss.
Though a small minority present with onset in the muscles of respiration, in the vast majority this is a feature of disease approaching its end stage following progression from other muscle groups. Respiratory failure is the most common cause of death.
Diagnosis of ALS
Though the diagnosis of ALS remains largely clinical, investigations can be helpful both in ruling out other disease processes as well as providing supportive findings.
Electromyography: findings consistent with both acute and
chronic denervation can be found. Also helps in the identification of fasciculation.
Nerve conduction studies: motor conduction can be normal or demonstrate abnormalities that reflect denervated muscles. Sensory conduction is normal
Genetics - als
May be organised in young patients and those with a family history of MND. The two most commonly identified mutations are C9orf72 and SOD1.
MRI - ALS
An MRI brain and spine may be ordered depending on the presentation, site of disease and considered differentials. Though MRI is preferred occasionally CT may be used.
Changes associated with ALS include increased signal on T2-weighted imaging of the corticospinal tracts.
ALS
Routine blood tests should be sent along with a blood borne virus screen (HIV, hepatitis B/C), vitamin B12, folate and creatine kinase.
Antibodies may be sent to try to rule out other neurological conditions. These include:
Acetylcholine receptor antibodies (to exclude myasthenia gravis)
Voltage-gated calcium-channel antibodies (to exclude Lambert-Eaton syndrome)
Anti-GM1 antibodies (to evaluate for multifocal mononeuropathy)
The revised El Escorial World Federation of Neurology criteria can be used to help diagnose ALS. As described in the paper by Brooks et al (2000), the diagnosis of ALS requires the presence of:
Evidence of LMN degeneration by clinical, electrophysiological or neuropathologic examination,
Evidence of UMN degeneration by clinical examination and
Progressive spread of symptoms or signs within a region or to other regions, as determined by history or examination
Together with the absence of:
Electrophysiological or pathological evidence of other disease processes that might explain the signs of LMN and/or UMN degeneration, and
Neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiological signs.
