Editing Motor neuron diseases (section)

== Diagnosis ==
Differential diagnosis can be challenging due to the number of overlapping symptoms, shared between several motor neuron diseases.<ref>{{Cite journal |last1=Statland |first1=Jeffrey M. |last2=Barohn |first2=Richard J. |last3=McVey |first3=April L. |last4=Katz |first4=Jonathan |last5=Dimachkie |first5=Mazen M. |date=2015 |title=Patterns of Weakness, Classification of Motor Neuron Disease & Clinical Diagnosis of Sporadic ALS |journal=Neurologic Clinics |volume=33 |issue=4 |pages=735–748 |doi=10.1016/j.ncl.2015.07.006 |issn=0733-8619 |pmc=4629510 |pmid=26515618}}</ref> Frequently, the diagnosis is based on clinical findings (i.e. LMN vs. UMN signs and symptoms, patterns of weakness), family history of MND, and a variation of tests, many of which are used to rule out disease mimics, which can manifest with identical symptoms.<ref>{{Cite web |title=Archive {{!}} Practical Neurology |url=https://pn.bmj.com/content/by/year |access-date=2022-06-24 |website=pn.bmj.com}}</ref><ref name=":12"/>

=== Classification ===
[[File:UMN vs LMN.png|thumb|296x296px|'''Corticospinal tract.''' Upper motor neurons originating in the primary motor cortex synapse to either lower motor neurons in the anterior horn of the central gray matter of the spinal cord (insert) or brainstem motor neurons (not shown). Motor neuron disease can affect either upper motor neurons (UMNs) or lower motor neurons (LMNs).]]
Motor neuron disease describes a collection of clinical disorders, characterized by progressive muscle weakness and the degeneration of the motor neuron on [[Electrophysiological techniques for clinical diagnosis|electrophysiological testing]]. The term "motor neuron disease" has varying meanings in different countries. Similarly, the literature inconsistently classifies which degenerative motor neuron disorders can be included under the umbrella term "motor neuron disease". The four main types of MND are marked (*) in the table below.<ref name=":8">{{Cite web|url=http://www.mndnsw.asn.au/about-mnd/what-is-mnd/44-mndforms.html|title=What forms does MND take?|website=mndnsw.asn.au|access-date=2018-12-11}}</ref>

All types of MND can be differentiated by two defining characteristics:<ref name=":7" />

# Is the disease sporadic or inherited?
# Is there involvement of the [[upper motor neuron]]s (UMN), the [[lower motor neuron]]s (LMN), or both?

Sporadic or acquired MNDs occur in patients with no family history of degenerative motor neuron disease. Inherited or genetic MNDs adhere to one of the following inheritance patterns: [[autosomal dominant]], [[Autosomal Recessive|autosomal recessive]], or [[X-linked]]. Some disorders, like ALS, can occur sporadically (85%) or can have a genetic cause (15%) with the same clinical symptoms and progression of disease.<ref name=":7" />

UMNs are motor neurons that project from the cortex down to the brainstem or spinal cord.<ref name=":4">{{Cite book|title=Neuroanatomy through clinical cases| vauthors = Blumenfeld H |date=2002 |publisher=Sinauer |isbn=087893060-4|location=Sunderland, Mass.|oclc=44628054}}</ref> LMNs originate in the anterior horns of the spinal cord and synapse on peripheral muscles.<ref name=":4" /> Both motor neurons are necessary for the strong contraction of a muscle, but damage to an UMN can be distinguished from damage to a LMN by physical exam.<ref>{{cite book | vauthors = Javed K, Daly DT | chapter = Neuroanatomy, Lower Motor Neuron Lesion |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK539814/ |title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969636 |access-date=2022-06-24 }}</ref>

{| class="wikitable"
 ! Type !! UMN degeneration !! LMN degeneration
|-
| colspan="3" |'''Sporadic MNDs'''
|-
| Sporadic amyotrophic lateral sclerosis (ALS)* || Yes<ref name=":7" />|| Yes<ref name=":7" />
|-
|Primary lateral sclerosis (PLS)* || Yes<ref name=":7" />|| No<ref name=":7" />
|-
|Progressive muscular atrophy (PMA)* || No<ref name=":7" />|| Yes<ref name=":7" />
|-
|Progressive bulbar palsy (PBP)* || Yes<ref name=":8" />|| Yes, [[bulbar]] region<ref name=":8" />
|-
|Pseudobulbar palsy|| Yes, bulbar region<ref name=":7" />|| No<ref name=":7" />
|-
|Monomelic amyotrophy (MMA)
|No
|Yes
|-
| colspan="3" |'''Inherited MNDs'''
|-
|Familial amyotrophic lateral sclerosis (ALS)*
|Yes<ref name=":7" />
|Yes<ref name=":7" />
|}

=== Tests ===
* [[Cerebrospinal fluid]] (CSF) tests: Analysis of the fluid from around the brain and spinal cord could reveal signs of an infection or inflammation.<ref name=":12">{{cite journal | vauthors = Foster LA, Salajegheh MK | title = Motor Neuron Disease: Pathophysiology, Diagnosis, and Management | journal = The American Journal of Medicine | volume = 132 | issue = 1 | pages = 32–37 | date = January 2019 | pmid = 30075105 | doi = 10.1016/j.amjmed.2018.07.012 | s2cid = 51910723 }}</ref>
* [[Magnetic resonance imaging]] (MRI): An MRI of the brain and spinal cord is recommended in patients with UMN signs and symptoms to explore other causes, such as a tumor, inflammation, or lack of blood supply (stroke).<ref name=":12" />
* [[Electromyography|Electromyogram]] (EMG) & [[nerve conduction study]] (NCS): The EMG, which evaluates muscle function, and NCS, which evaluates nerve function, are performed together in patients with LMN signs.
* For patients with MND affecting the LMNs, the EMG will show evidence of: (1) acute denervation, which is ongoing as motor neurons degenerate, and (2) chronic denervation and [[reinnervation]] of the muscle, as the remaining motor neurons attempt to fill in for lost motor neurons.<ref name=":12" />
* By contrast, the NCS in these patients is usually normal. It can show a low [[compound muscle action potential]] (CMAP), which results from the loss of motor neurons, but the [[sensory neuron]]s should remain unaffected.<ref>{{cite journal | vauthors = Duleep A, Shefner J | title = Electrodiagnosis of motor neuron disease | journal = Physical Medicine and Rehabilitation Clinics of North America | volume = 24 | issue = 1 | pages = 139–151 | date = February 2013 | pmid = 23177036 | doi = 10.1016/j.pmr.2012.08.022 }}</ref>
* [[Tissue biopsy]]: Taking a small sample of a muscle or nerve may be necessary if the EMG/NCS is not specific enough to rule out other causes of progressive muscle weakness, but it is rarely used.