So let's talk a little bit more about ALS
and look at some of the differential
diagnoses that we need to consider in patients
presenting with this type of pathology.
Sporadic degenerative conditions
like ALS are a consideration,
but we also need to think about
structural lesions in the spine,
degenerative or hereditary changes,
vascular pathology, metabolic causes,
autoimmune or disimmune causes, infection
myopathic, or neuromuscular junction disorders
can present with patients who have
primary lower motor neuron findings,
which was not present in our patient.
And then malignant or paraneoplastic disorders
and some others need to be considered.
So it's a very broad differential diagnosis and the
workup of these patients is often quite extensive
Again, because there's not a test or
a diagnostic investigation to confirm
ALS or motor neuron disease, and so we're
really left to rule out alternative etiologies.
So let's walk through each of these and
talk about some of these groups of disorders,
and the names of the conditions that present
with upper and lower motor neuron findings,
pure upper motor neuron findings and
then pure lower motor neuron findings.
The first group are the sporadic
motor neuron diseases, and this is ALS.
These are motor neuron
disorders, they're sporadic in onset,
they're degenerative in their pathophysiology.
They begin over a chronic
period and progress relentlessly.
And the classic example is ALS or
amyotrophic lateral sclerosis which involves
both a combination of upper and lower motor
neuron findings as was present in our case.
There's a pure upper motor
variant - primary lateral sclerosis
which is the same thing as ALS, just
only the upper motor neuron findings
and not the lower motor neuron findings.
There's also pure lower motor neuron variants.
Progressive muscle atrophy, juvenile
monomelic atrophy, brachial amyotrophic diplegia
and leg amyotrophic diplegia which are quite rare.
And they're just lower motor neuron variants.
They present with primarily
lower motor neuron findings.
Moving on, let's move to a different group of
disorders that can masquerade as motor neuron disease.
The first is metabolic, nutritional and
toxic disorders and these are very important
to evaluate in these patients.
Patients that present with a combination
of upper and lower motor neuron findings
could have hyperthyroidism,
hyperparathyroidism, B12, or copper deficiency
and so those are things that
we routinely test in these patients.
Pure upper motor neuron variants include
B12, copper deficiency and vitamin D deficiency.
Vitamin D deficiency presenting with
a myeloneuropathy often with ataxia.
And then pure lower motor neuron
variants that are metabolic, nutritional or toxic
include heavy metal exposure, and this can cause
a motor predominant lower motor neuron disorder.
And a classic would be lead or plumbism
which presents with motor predominant symptoms
that is lower motor neuron in its presentation.
What about some other groups of diseases.
Let's talk about some structural
conditions that can present in this way.
Iin terms of combined upper and lower motor
neuron symptoms, brainstem tumors or masses
particularly at the caudal aspect of the
medulla can present with a combination of
of upper and some lower motor neuron symptoms
spinal cord tumors and other spinal cord lesions.
Cervical Spondylosis is very important
and would be evaluated in our patient
with an MRI of the cervical cord.
Some polyradiculopathies and
plexopathies so they really present more with
a lower motor neuron variant of disease.
And then syringomyeloia can present with both
upper motor neuron and lower motor neuron findings
when severe syringomyelia or a syrinx is a
fluid collection in the internal part of the cord.
This is the most common just
classic central cord syndrome.
So patients present with a predominance of upper
motor neuron symptoms and upper extremity symptoms
often with early bowel-bladder dysfunction, and it
can present similarly as a motor neuron disease.
When we think about some of the
pure upper motor neuron variants,
spinal cord tumors, cervical
spondylosis, foramen magnum tumor,
chiari malformation and a
syrinx should be on the differential
and then some of the pure lower motor neuron
variants poly radiculopathy, and plexopathy.
There are some infections that we shouldn't
consider on the differential diagnosis for ALS.
Two infections that can present with a
combination of upper and lower motor neuron findings
are HIV myelopathy and Lyme disease,
which are important to test for in these patients.
And sometimes neurosyphilis and tropical
spastic paraparesis, or from HTLV infection
can present in patients with potential exposures.
There are a number of degenerative and hereditary
conditions that are also on the differential diagnosis
for motor neuron disease, Poly glucosan body
disease, hereditary ALS and the leukodystrophies
are some of the combined upper
motor or lower motor neuron syndromes.
Heredity spastic paraparesis presents
with pure upper motor neuron symptoms
and then spinal muscle atrophy, and then a
couple other more rare disease can present as
pure lower motor neuron variants.
We also need to think about
immune system disorders.
And when we think about the pure
upper motor neuron presentations,
MS is a central nervous system disorder.
Patients present with upper motor neuron findings
and in the appropriate clinical presentation,
the evidence of multiple inflammatory
lesions in the brain or spinal cord
would point towards a
diagnosis of MS for these patients.
Stiff person syndrome is also an inflammatory
disorder where patients become progressively stiff
and spastic and this is a result of typically
antibody deposition within the central nervous system.
Classically, GAD antibody is
associated with this syndrome,
which is on the differential diagnosis for an
upper motor neuron predominant presentation.
Multifocal motor neuropathy - mononeuritis
multiplex and CIDP are considerations
for lower motor neuron syndromes.
Strokes and vascular mouth
abnormalities can masquerade as ALS,
particularly multiple cerebral
infarct such as with a vasculitis.
There are some malignancies we
need to consider such as lymphoma.
And then some other
considerations, some other disorders -
post radiation plexopathy can cause
primary motor neuron dysfunction,
and then some other conditions
affecting other areas of the nervous system.
Myopathies and neuromuscular junction
diseases, those typically present with
lower motor neuron predominant presentations.
Inclusion body myositis, Myasthenia
gravis Polymyositis and these other conditions
that are important to evaluate for patients with
lower motor neuron predominant presentations.