Upper and Lower Motor Neuron Diseases: Differential Diagnosis

00:01 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.

00:10 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.

00:35 And then malignant or paraneoplastic disorders and some others need to be considered.

00:39 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.

00:56 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.

01:10 The first group are the sporadic motor neuron diseases, and this is ALS.

01:14 These are motor neuron disorders, they're sporadic in onset, they're degenerative in their pathophysiology.

01:20 They begin over a chronic period and progress relentlessly.

01:24 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.

01:35 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.

01:45 There's also pure lower motor neuron variants.

01:48 Progressive muscle atrophy, juvenile monomelic atrophy, brachial amyotrophic diplegia and leg amyotrophic diplegia which are quite rare.

01:57 And they're just lower motor neuron variants.

01:59 They present with primarily lower motor neuron findings.

02:04 Moving on, let's move to a different group of disorders that can masquerade as motor neuron disease.

02:09 The first is metabolic, nutritional and toxic disorders and these are very important to evaluate in these patients.

02:17 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.

02:30 Pure upper motor neuron variants include B12, copper deficiency and vitamin D deficiency.

02:35 Vitamin D deficiency presenting with a myeloneuropathy often with ataxia.

02:41 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.

02:52 And a classic would be lead or plumbism which presents with motor predominant symptoms that is lower motor neuron in its presentation.

03:00 What about some other groups of diseases.

03:02 Let's talk about some structural conditions that can present in this way.

03:06 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.

03:21 Cervical Spondylosis is very important and would be evaluated in our patient with an MRI of the cervical cord.

03:28 Some polyradiculopathies and plexopathies so they really present more with a lower motor neuron variant of disease.

03:36 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.

03:48 This is the most common just classic central cord syndrome.

03:51 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.

04:04 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.

04:20 There are some infections that we shouldn't consider on the differential diagnosis for ALS.

04:25 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.

04:34 And sometimes neurosyphilis and tropical spastic paraparesis, or from HTLV infection can present in patients with potential exposures.

04:44 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.

04:59 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.

05:13 We also need to think about immune system disorders.

05:16 And when we think about the pure upper motor neuron presentations, MS is a central nervous system disorder.

05:21 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.

05:34 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.

05:45 Classically, GAD antibody is associated with this syndrome, which is on the differential diagnosis for an upper motor neuron predominant presentation.

05:54 Multifocal motor neuropathy - mononeuritis multiplex and CIDP are considerations for lower motor neuron syndromes.

06:03 Strokes and vascular mouth abnormalities can masquerade as ALS, particularly multiple cerebral infarct such as with a vasculitis.

06:11 There are some malignancies we need to consider such as lymphoma.

06:15 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.

06:27 Myopathies and neuromuscular junction diseases, those typically present with lower motor neuron predominant presentations.

06:34 Inclusion body myositis, Myasthenia gravis Polymyositis and these other conditions that are important to evaluate for patients with lower motor neuron predominant presentations.