Amyotrophic lateral sclerosis (ALS) is
life threatening disorder characterized by progressive loss of the upper and
lower motor neurons at the spinal or bulbar level. It was described in 1869 by a
French neurologist Jean Martin Charcot. It also known as Lou Gehrig’s disease.
Some others use the term motor neuron disease for a group of conditions of
which ALS is the most common. There is no significant causing for it, but some
researchers found some factors increase its incidence such as genetic factors,
HIV patients and head trauma (Kiernan et al, 2011).
This paper will discusses definition,
pathophysiology, cardinal subjective and objective finding, anatomy and
physiology correlated with clinical features, contrast
diagnosis, prognosis, medical and surgical management of motor neurons disease.
Definition and pathogenesis of ALS
ALS is an
idiopathic condition of upper and lower motor neurons death in the motor cortex
of the brain, brain stem and spinal cord. The death of motor neurons start by
developing of protein inclusion in cell bodies and axons. This may be partly
due to defects in protein degradation. These inclusions often contain ubiquitin
and generally incorporate one of the ALS associated proteins (SOD1, TAR DNA
binding protein (TDP-43) or FUS). The mutation of SOD1 may also contribute to
motor neuron cell death through generating free radicals. The inclusion of
developing protein causes excitotoxicity and cell death by high levels of
intracellular calcium caused by increased activity of excitatory neurotransmitters
(Rothstein, 2009). This concept has been supported by increased glutamate and
dysfunctional glutamate transporter RNA in cerebrospinal fluid of those with
ALS (Zarei et al, 2015). This is further supported by the only effective
treatment being an anti-glutamatergic drug (Riluzole), as well as the poor
ability to buffer calcium in motor neurons relative to other neurons. In SOD1 patients, possibly interfere with
axonal transport, leading to cell death from SOD1 toxicity (Foran& Trotti,
symptoms and prognosis.
The identi?cation of
speci?c types benefits the patients with regards to prognosis and survival. The
main presentations of ALS include:
(1) Limb onset ALS with a
combination of upper and lower motor neuron (UMN and LMN) involving a
degeneration of motor cells in cortical, brainstem and spinal cord (Kiernan et
al, 2011). Patients experience awkwardness when walking or running or even
tripping over or stumbling. Some patients walking with a “dropped
foot” which drags gently on the ground. Moreover, individuals complain
difficulty with tasks require manual handing such as buttoning a shirt, writing,
or turning a key in a lock (Gordon et al, 2004).
(2) Bulbar onset leads to
face, mouth, and throat muscles weakness first because motor neurons in the
medulla oblongata start to die first along with lower motor neurons (Kiernan et
al, 2011). It presenting with dysarthria, dysphagia and limb weakness
(3) Primary lateral sclerosis with pure UMN
(4) Progressive muscular
atrophy with pure LMN involvement.
In about 5% of ALS patients trunk muscles
affected first and respiratory involvement later. In all cases the disease
spreads and affects other regions. The symptoms may also be limited to one
spinal region. Atypical modes of presentation can include weight loss, muscles cramps
and fasciculation. Around half of people with ALS experience mild changes in
cognitive and behaviour and 10–15% show signs of frontotemporal dementia
(Hobson , 2016). Sensory nerves and the autonomic nervous system
are generally unaffected.
The disease progression
vary from person to person. In later stages of ALS, aspiration pneumonia can
develop, and maintaining a healthy weight is a significant problem require
insertion of a feeding tube. As the diaphragm, intercostal muscles and other
respiratory muscles became weaken, most of patients die by respiratory failure
(Kiernan et al, 2011).
ALS Diagnosis and Management
Doctors take person’s full
medical history and usually conduct a neurologic examination with a regular
intervals to assess the worsening of symptoms such as muscle weakness, atrophy,
spasticity and hyperreflexia (Kiernan et al, 2011).
Because symptoms of ALS can be similar to
other diseases, appropriate tests must be conducted to differentiate the
diagnosis. One of these tests is electromyography (EMG) to assess muscle’s
electrical activity. EMG findings support the diagnosis of ALS. Another common
test measures nerve conduction velocity (NCV). Specific abnormalities in the
NCV results from peripheral neuropathy or myopathy rather than ALS. Magnetic
resonance imaging (MRI) is normal in people with early stage of ALS. However,
MRI indicate evidence of other problems causing the symptoms such as a spinal
cord tumour, multiple sclerosis, cervical disk herniation or cervical
spondylosis (Berkhemer et al, 2015).
Based on the person’s symptoms and examination
findings and tests. Then the physician order tests on blood and urine samples
to eliminate the possibility of other diseases.
In some cases of contrast diagnosis between myopathy and ALS, a muscle
ALS need to differentiate
from the ALS mimic syndromes. ALS mimic syndromes have a similar clinical features of
ALS. Myasthenia syndrome also known as
Lambert Eaton syndrome. It copyist ALS and its initial presentation can be
similar to that of myasthenia gravis (MG). Autoimmune disease sometimes mixed
with ALS diagnosis. Benign fasciculation syndrome is another condition that copyist
some of the early symptoms of ALS but is accompanied by normal EMG readings and
no major disablement (Silani et al, 2011).
One study examined 190
people of ALS diagnostic criteria, complemented with laboratory research. Thirty of these people had their diagnosis
completely changed during the clinical observation. In the same study, three
people had a positive diagnosis of MG first, leading to a delay in diagnosis
and treatment. MG is treatable but ALS is not (Chieia et al, 2010).
Management of ALS attempts to relieve
symptoms and extend life expectancy. This supportive care is best provided by multidisciplinary
teams of healthcare professionals working to keep the patient mobile and
comfortable as possible.
The table (1) show the palliative
management of ALS patients. The Riluzole, Baclofen and glycopyrrolate are some
medications used to easing and reduce the symptoms of ALS disease. More
specifically, Riluzole work to Blocking the release of the excitatory
neurotransmitters. The reduction in activity prevents the ruining of the neuronal
muscle. Baclofen Prescribed to control the spasticity and glycopyrrolate Prescribed
when ALS patients having trouble swallowing their saliva (Zarei et al, 2015).
One of 2016 review of stem cell therapy
trials found evidence that “intra spinal stem cell implantation was relatively
safe and possibly effective” (Chen et al, 2016).
Stem cell therapy shown to help prolong
survival and control the symptoms associated with ALS. This method include neurotrophic
factors and insulin like growth factor. Both those proteins are still under
clinical trials and need to be further studied to evaluate their efficiency and
associated side effects (Bensimon et al, 1994).
“Let us keep looking, in spite of
everything. Let us keep searching. It is indeed the best method of ?nding, and
perhaps thanks to our e?orts, the verdict we will give such a
patient tomorrow will not be the same we must give this man today.” Charcot
ALS is a sporadic fatal disease. It is a
general muscles weakness with its further complication. ALS require more of
research, study and trials. There is no treatment for it but ALS patient take a
health care to maintain longer life span and survive.