In this talk, we're going to
review motor neuron diseases.
And let's start with a case.
It's a case of a 56 year old,
presenting with left extremity weakness.
A 56-year old woman with past medical
history of hypertension and hyperlipidemia
presents with left extremity weakness.
This initially began in January with
weakness in her left foot and ankle.
This remained stable until a
motor vehicle accident in April.
The patient was evaluated
for a whiplash injury at that time.
2 to 3 weeks following the accident, the
patient noticed weakness progressing up the leg.
As of July, the patient had
developed weakness in the left hand.
By October, the patient has started to use
a walker and then a wheelchair to ambulate.
And in December, the patient presented
with inability to grasp in the left arm,
and atrophy of the hand muscles.
So we're seeing in this case, a steadily
and relentlessly progressive illness
that initially was thought to be
due to this motor vehicle accident,
but clearly is due to other underlying pathology.p
So let's look at some of the key features.
First of all, the distribution.
This is left hemibody symptoms which could
localize to a number of areas of the nervous system,
central and peripheral nervous system.
We don't know the reflex exam, and that will
be important to focus on in our examination,
as well as sensory findings in this
patient to figure out exactly where
we localize these symptoms to.
And an important wildcard here is
this gradual progression of symptoms
which support a degenerative etiology, perhaps
some rare inflammatory or infectious conditions,
but really raise suspicion for a
degenerative or inherited or congenital etiology
that may be going on for this patient.
And then potentially a neoplasm, which could
present with slow insidious onset of symptoms,
particularly for from a benign lesion.
In this case there were no bulbar symptoms, no sensory
loss, no neck pain, no bowel-bladder dysfunction
and some chronic lower back pain
that is likely unrelated to the symptoms
that are leading to their presentation.
And importantly, bulbar symptoms
would point us to the brainstem.
Sensory loss would suggest the presence
of sensory peripheral nerve involvement
or sensory fiber involvement
in the central nervous system.
No neck pain suggests no degenerative changes in the
spine that may be clearly offending in this case,
and the lack of bowel bladder dysfunction is
something we could see with a central cord syndrome.
So where do we localize these symptoms to?
Well, like any neurologic presentation, we
walk through those areas of the nervous system,
it could be in the cortex or subcortex.
But importantly, motor and sensory fibers
often run together in the cortex or sub cortex.
And this is really a motor
There's no sensory symptoms.
Could be the brainstem, that's
the next level down in layer.
But again, motor and sensory
fibers travel in close proximity, and so
it has to be very localized to
a specific part of the brainstem
and a degenerative or neoplastic or inherited
syndrome in the brainstem would be quite atypical
to present with that focal and localized symptoms.
What about the spinal cord?
It could be a spinal cord problem, there are
no bulbar symptoms, no cortical symptoms,
the spinal cord is a consideration but
again, we don't see sensory changes
and sensory changes would be
common in various spinal cord disorders.
Peripheral nerve, could it be peripheral nerve?
It had to be a lot of peripheral nerves, the
peripheral nerves to the leg, and to the arm and
and throughout the entire
hemibody, which is quite atypical,
but we are hearing some symptoms that
could suggest a peripheral nerve pathology.
We're not hearing things that suggest
neuromuscular junction, or muscle
but important considerations and patients
presenting with motor predominant symptoms.
So let's take a closer look at
this patient's physical exam.
Her mental status was intact
and cranial nerves were also intact,
really putting brain subcortex and
brainstem lower on our differential diagnosis
or localization for this patient.
What about motor function?
Strength exam showed left upper
extremity weakness - 3 out of 5,
Strength is at two out of five in the
dorsal interosseous muscles in the hand.
The left lower extremity showed 3+ out of 5,
Strength also weak to all muscle
groups throughout the left lower extremity.
And right upper and right lower
extremity were full 5 out of 5 strength.
We're seeing that clear asymmetry
in this patient's presentation.
Bulk showed significant atrophy in the
left hand telling us that this weakness,
this problem had been going
on for some period of time
and likely is involving the
peripheral nervous system.
Reflexes were 3+ throughout,
upper and lower extremities bilaterally
which is telling us there's also some
central nervous system component to this.
And sensation was intact
throughout, which is quite surprising.
With this this degree of weakness
and these changes with reflexes,
the presence of no sensory findings really
point towards a motor-predominant disorder
or a motor neuronopathy, the
motor neurons appear to be affected
Fasciculations are present within
the left arm in multiple muscle groups
and less frequently in the right arm.
Fasciculations are a peripheral nervous
system or lower motor neuron finding
and really point towards
lower motor neuron pathology.
So we're seeing both upper
and lower motor neuron findings.
So how would you characterize this condition?
Is this an upper motor neuron
disorder, a lower motor neuron disorder,
a combined upper and lower motor neuron
disorder or an extrapyramidal disorder?
Well, this is really important
to pick out of this case.
This is not just an upper motor neuron
disorder, there's the presence of fasciculations
which is indicative of lower motor neuron findings.
It's not just a lower motor neuron
disorder, there's hyperreflexia throughout,
which is indicative of upper motor neuron findings.
It's not extrapyramidal.
The classic extrapyramidal disorder is
Parkinsonism, which presents with bradykinesia,
postural instability, rigidity with or without tremor,
and we have none of those findings in this case
This is a pyramidal problem,
the pyramidal system is affected.
And it's really a classic presentation of
combined upper and lower motor neuron findings.
And in this case, we have upper motor
neuron findings in the same location, same level,
spinal level as our lower motor neuron findings which
is highly suggestive of a motor neuron disorder.
So let's look at the workup for this patient
which was quite extensive to look into
all the potential causes of this presentation.
First, we see an MRI of the cervical spine.
This is a T2 sagittal image which shows some
very mild degenerative changes in the cervical spine
which do not explain this presentation.
And essentially, the MRIs of the C spine is
unremarkable for an etiology of this disorder.
The patient underwent MRI of the brain to
look for any central nervous system pathology
that could be contributing.
And as this as expected, the MRI of the brain was
unremarkable and again did not show any explanation
for this patients combined upper
and lower motor neuron disorder.
There was also an extensive laboratory
investigation that was undergone.
CK was normal at 53 though sometimes
can be mildly elevated in this condition.
ESR and CRP were performed to look for any
systemic inflammatory processes that could be
contributing to a secondary CNS
inflammatory disorder which were norma
ANA was negative, Thyroid
Stimulating Hormone - negative,
Serum protein electrophoresis was without
an M spike, there was no paraproteinemia,
free light chains were within
normal limits and RPR was negative.
In addition, the patient underwent B12 testing.
B12 can present as a myeloneuropathy
central nervous system or spinal cord pathology
and peripheral neuropathy.
So combined upper and lower motor
neuron symptoms but was normal at 533 (pg/mL).
Copper level was also
performed and within normal limits
and both B 12 deficiency and copper
deficiency can present as a myeloneuropathy.
Lyme disease testing was negative, Vitamin E
was within normal limits and that can present with
again a myeloneuropathy with ataxia,
which was a consideration in this
case in this patient but was normal,
and then HIV testing was negative.
So the patient underwent EMG nerve
conduction study to further evaluate
the potential cause for this condition and it
was consistent with motor neuron disease.
The left median motor and ulnar
motor responses revealed low amplitude
so something's going on to reduce the
number of nerves, the number of peripheral nerves
to the left median and ulnar nerves.
All sensory studies were intact with
normal values, and that's really important.
There's no diagnostic test
for motor neuron disease.
It's a diagnosis of exclusion, and excluding
the presence of sensory abnormalities is critical.
Motor neuron diseases, disease of the motor neurons,
not the sensory neurons and we see that here.
And needle EMG showed abnormal
spontaneous activity with obvious neurogenic pattern
with activation on all four extremities
that we're seeing denervation changes,
loss of innervation of the muscles as a result of
some motor neuron pathology on needle EMG exam.
And so ultimately, this patient's presentation was
consistent with a diagnosis of motor neuron disease,
or ALS, amyotrophic lateral sclerosis.
And so let's walk through some of the
key features of motor neuron disease,
how we define it, localize it,
evaluate and treat this disorder.
First, let's talk about how we define motor neuron
disease, both the upper and lower motor neurons.