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{{short description|Group of neurological disorders affecting motor neurons}}
{{Infobox_Disease |
{{about|a group of muscle-wasting disorders|the disease amyotrophic lateral sclerosis, also known as motor neuron(e) disease|Amyotrophic lateral sclerosis}}
Name = Motor neurone disease |
{{Use dmy dates|date=March 2023}}
Image = |
{{Infobox medical condition
Caption = |
| name = Motor neuron disease
DiseasesDB = 8358 |
ICD10 = {{ICD10|G|12|2|g|10}} | | image = Polio spinal diagram-en.svg
ICD9 = {{ICD9|335.2}} | | caption = spinal diagram
ICDO = | | field = ]
OMIM = | | synonyms =
MedlinePlus = | | symptoms =
| complications =
eMedicineSubj = |
| onset =
eMedicineTopic = |
| duration =
MeshName = Motor+Neuron+Disease |
MeshNumber = C10.574.562 | | types =
| causes =
| risks =
| diagnosis =
| differential =
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
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}} }}
The '''motor neurone diseases''' (or '''motor neuron diseases''') (MND) are a group of progressive neurological disorders that destroy ]s, the cells that control voluntary muscle activity such as speaking, walking, breathing, and swallowing.


'''Motor neuron diseases''' or '''motor neurone diseases''' ('''MNDs''') are a group of rare ] disorders that selectively affect ]s, the cells which control ] of the body.<ref name=El2008/><ref name="NINDS2014">{{cite web|title=Motor Neuron Diseases Fact Sheet: National Institute of Neurological Disorders and Stroke (NINDS)|url=http://www.ninds.nih.gov/disorders/motor_neuron_diseases/detail_motor_neuron_diseases.htm|publisher=ninds.nih.gov|url-status=dead|archive-url=https://web.archive.org/web/20140413093035/http://www.ninds.nih.gov/disorders/motor_neuron_diseases/detail_motor_neuron_diseases.htm|archive-date=13 April 2014|access-date=7 November 2010}}</ref> They include ] (ALS),<ref name="NHS">{{cite web |title=Motor neurone disease – NHS |url=https://www.nhs.uk/conditions/motor-neurone-disease/ |website=nhs.uk |access-date=24 October 2020 |language=en |date=15 January 2018}}</ref><ref name="healthdirectAU">{{cite web | author = Healthdirect Australia |title=Motor neurone disease (MND) |url=https://www.healthdirect.gov.au/motor-neurone-disease-mnd |website=healthdirect.gov.au |access-date=24 October 2020 |language=en-AU |date=17 April 2020}}</ref> ] (PBP), ], ] (PMA), ] (PLS), ] (SMA) and ] (MMA), as well as some rarer variants resembling ALS.
==Forms==
Forms of motor neurone disease include:
* ] (ALS) (sometimes called ]'s disease)
* ] (PMA)
* ] (SMA)
* ]
* ]
* ]


Motor neuron diseases affect both children and adults.<ref name=":14" /> While each motor neuron disease affects patients differently, they all cause movement-related symptoms, mainly ].<ref name=":7" /> Most of these diseases seem to occur randomly without known causes, but some forms are inherited.<ref name="NINDS2014" /> Studies into these inherited forms have led to discoveries of various ]s (e.g. '']'') that are thought to be important in understanding how the disease occurs.<ref name=":2">{{Cite book|title=Clinical and molecular aspects of motor neuron disease| vauthors = Cooper-Knock J, Jenkins T, Shaw PJ |isbn=9781615044290|location=San Rafael, California (1537 Fourth Street, San Rafael, CA 94901 USA)|oclc=860981760|name-list-style=vanc|date = 2013-09-01}}</ref>
==Terminology==
In this article, MND refers to a group of diseases which affect the motor neurones. In the ], the term ] is more commonly used, where it is also known as ]'s disease, after the ] player. Although previously described by other neurologists of the 19th century, it was ], a ] ], who suggested grouping together a number of disparate conditions all affecting the ] of the spinal cord in ]. In France the disease is sometimes known as Maladie de Charcot (Charcot's disease), although it may also be referred to by the direct translation of ALS, Sclerose Laterale Amyotrophique (SLA). To help prevent confusion, the annual scientific research conference dedicated to the study of MND is called the International ALS/MND Symposium.


Symptoms of motor neuron diseases can be first seen at birth or can come on slowly later in life. Most of these diseases worsen over time; while some, such as ALS, shorten one's life expectancy, others do not.<ref name="NINDS2014" /> Currently, there are no approved treatments for the majority of motor neuron disorders, and care is mostly symptomatic.<ref name="NINDS2014" />
==Signs and symptoms==
Neurological examination presents specific signs associated with upper and lower motor neurone degeneration. Signs of ] damage include ], brisk ] and the ]. Signs of ] damage include weakness and muscle atrophy.


== Signs and symptoms ==
Note that every muscle group in the body requires both upper and lower motor neurones to function. It is a common misconception that "upper" motor neurones control the arms, whilst "lower" motor neurones control the legs. The signs described above can occur in any muscle group, including the arms, legs, torso, and bulbar region.
] (ALS). (A) He needs assistance to stand. (B) Advanced atrophy of the tongue. (C) There is upper limb and truncal muscle atrophy with a positive ]. (D) Advanced ] atrophy.<ref>{{Cite web|title=Patient with amyotrophic lateral sclerosis (ALS) (case {{!}} Open-i|url=https://openi.nlm.nih.gov/detailedresult.php?img=3996815_bmjopen2013004353f02&query=amyotrophic+lateral+sclerosis&it=xg&lic=by&req=4&npos=5|website=openi.nlm.nih.gov|url-status=dead|archive-url=https://web.archive.org/web/20181215225214/https://openi.nlm.nih.gov/detailedresult.php?img=3996815_bmjopen2013004353f02&query=amyotrophic+lateral+sclerosis&it=xg&lic=by&req=4&npos=5|archive-date=15 December 2018|access-date=2018-12-12}}</ref>]]
Signs and symptoms depend on the specific disease, but motor neuron diseases typically manifest as a group of movement-related symptoms.<ref name=":7">{{cite journal | vauthors = Statland JM, Barohn RJ, McVey AL, Katz JS, Dimachkie MM | title = Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis | journal = Neurologic Clinics | volume = 33 | issue = 4 | pages = 735–748 | date = November 2015 | pmid = 26515618 | pmc = 4629510 | doi = 10.1016/j.ncl.2015.07.006 }}</ref> They come on slowly, and worsen over the course of more than three months. Various patterns of muscle weakness are seen, and muscle cramps and spasms may occur. One can have difficulty breathing with climbing stairs (]), difficulty breathing when lying down (]), or even ] if breathing muscles become involved. ] symptoms, including difficulty speaking (]), difficulty swallowing (]), and excessive saliva production (]), can also occur. Sensation, or the ability to feel, is typically not affected. Emotional disturbance (e.g. ]) and cognitive and behavioural changes (e.g. problems in word fluency, decision-making, and memory) are also seen.<ref name="NINDS2014" /><ref name=":7" /> There can be lower motor neuron findings (e.g. muscle wasting, muscle twitching), upper motor neuron findings (e.g. brisk reflexes, ], ], increased muscle tone), or both.<ref name=":7" />


Motor neuron diseases are seen both in children and adults.<ref name="NINDS2014" /> Those that affect children tend to be inherited or familial, and their symptoms are either present at birth or appear before learning to walk. Those that affect adults tend to appear after age 40.<ref name="NINDS2014" /> The clinical course depends on the specific disease, but most progress or worsen over the course of months.<ref name=":7" /> Some are fatal (e.g. ALS), while others are not (e.g. PLS).<ref name="NINDS2014" />
Symptoms usually present between the ages of 50-70, and include progressive weakness, muscle wasting, and muscle ]s; spasticity or stiffness in the arms and legs; and overactive tendon reflexes. Patients may present with symptoms as diverse as a dragging foot, unilateral muscle wasting in the hands, or slurred speech.


=== Patterns of weakness ===
The symptoms described above may resemble a number of other rare diseases, known as "MND Mimic Disorders". These include, but are not limited to ], ], ], ] and ]. A small subset of familial MND cases occur in children, such as "juvenile ALS", Madras syndrome, and individuals who have inherited the ALS2 gene. However, these are not typically referred to as MND, but by their specific names.
Various patterns of muscle weakness occur in different motor neuron diseases.<ref name=":7" /> Weakness can be symmetric or asymmetric, and it can occur in body parts that are distal, proximal, or both. According to Statland et al., there are three main weakness patterns that are seen in motor neuron diseases, which are:<ref name=":7" /><ref>{{cite journal | vauthors = Barohn RJ, Amato AA | title = Pattern-recognition approach to neuropathy and neuronopathy | journal = Neurologic Clinics | volume = 31 | issue = 2 | pages = 343–361 | date = May 2013 | pmid = 23642713 | pmc = 3922643 | doi = 10.1016/j.ncl.2013.02.001 }}</ref>


# Asymmetric distal weakness without sensory loss (e.g. ALS, PLS, PMA, MMA)
==Diagnosis==
# Symmetric weakness without sensory loss (e.g. PMA, PLS)
The diagnosis of MND is a clinical one, established by a neurologist on the basis of history and neurological examination. There is no diagnostic test for MND. Investigations such as blood tests, ] (EMG), ] (MRI), and sometimes ] are useful to rule out other disorders that may mimic MND. However, the diagnosis of MND remains a clinical one. Having excluded other diseases, a relatively rapid progression of symptoms is a strong diagnostic factor. Although an individual's progression may sometimes "plateau", it will not recover or slow down. A set of diagnostic criteria called the El Escorial criteria have been defined by the World Federation of Neurologists for use in research, particularly as inclusion/exclusion criteria for clinical trials. Due to a lack of clinical diagnostic criteria, some neurologists use the El Escorial criteria during the diagnostic process, although strictly speaking this is ].
# Symmetric focal midline proximal weakness (neck, trunk, bulbar involvement; e.g. ALS, PBP, PLS)


=== Lower and upper motor neuron findings ===
MND in the presence of both upper and lower motor neurone degeneration is ALS. Where the illness affects only the upper motor neurones it is PLS, and where it affects only the lower motor neurones it is PMA. Progressive bulbar palsy is degeneration of the lower motor neurones innervating the bulbar region (mouth, face, and throat), whilst pseudobulbar palsy refers to degeneration of the upper motor neurones to the same region.
Motor neuron diseases are on a spectrum in terms of upper and lower motor neuron involvement.<ref name=":7" /> Some have just lower or upper motor neuron findings, while others have a mix of both. Lower motor neuron (LMN) findings include muscle ] and ]s, and upper motor neuron (UMN) findings include ], spasticity, muscle spasm, and abnormal reflexes.<ref name="NINDS2014" /><ref name=":7" />


Pure upper motor neuron diseases, or those with just UMN findings, include PLS.<ref>{{cite book | vauthors = Emos MC, Agarwal S | chapter = Neuroanatomy, Upper Motor Neuron Lesion |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK537305/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30725990 |access-date=2022-06-24 }}</ref>
==Prognosis==
Most cases of MND progress quite quickly, with noticeable decline occurring over the course of months. Although symptoms may present in one region, they will typically spread. If restricted to one side of the body they are more likely to progress to the same region on the other side of the body before progressing to a new region. After several years, most patients require help to carry out activities of daily living such as self care, feeding, and transportation.


Pure lower motor neuron diseases, or those with just LMN findings, include PMA.<ref>{{Cite web |title=Progressive Muscular Atrophy – an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/neuroscience/progressive-muscular-atrophy |access-date=2022-06-24 |website=sciencedirect.com}}</ref>
MND is typically fatal within 2-5 years. Around 50% die within 14 months of diagnosis. The remaining 50% will not necessarily die within the next 14 months as the distribution is significantly skewed. As a rough estimate, 1 in 5 patients survive for 5 years, and 1 in 10 patients survive 10 years. ] is a well-known example of a person with MND, and has lived for more than 40 years with the disease.


Motor neuron diseases with both UMN and LMN findings include both familial and sporadic ALS.<ref>{{Cite web |title=Motor Neuron Diseases Fact Sheet {{!}} National Institute of Neurological Disorders and Stroke |url=https://www.ninds.nih.gov/health-information/patient-caregiver-education/fact-sheets/motor-neuron-diseases-fact-sheet |access-date=2022-06-24 |website=ninds.nih.gov}}</ref>
Mortality results when the muscles that control breathing are no longer able to expel carbon dioxide. One exception is PLS, which may last for upwards of 25 years. Given the typical age of onset, this effectively leaves most PLS patients with a normal life span. PLS can progress to ALS, decades later.


==Pathology== == Causes ==
Most cases are sporadic and their causes are usually not known.<ref name="NINDS2014" /> It is thought that environmental, toxic, viral, or genetic factors may be involved.<ref name="NINDS2014" />
===Causes===
About 90% of cases of MND are "sporadic", meaning that the patient has no family history of ALS and the case appears to have occurred with no known cause. Genetic factors are suspected to be important in determining an individual's susceptibility to disease, and there is some weak evidence to suggest that onset can be "triggered" by as yet unknown environmental factors (see 'Epidemiology' below).
Approximately 10% of cases are "familial MND", defined either by a family history of MND or by testing positive for a known genetic mutation associated with the disease. The following genes are known to be linked to ALS: Cu/Zn superoxide dismutase ''SOD1'', ''ALS2'', ''NEFH''(a small number of cases), senataxin (SETX) and vesicle associated protein B (''VAPB'').


===DNA damage===
Of these, SOD1 mutations account for some 20% of familial MND cases. The ''SOD1'' gene codes for the enzyme ], a ] scavenger that reduces the ] of cells throughout the body. So far over 100 different mutations in the SOD1 gene have been found, all of which cause some form of ALS(). In North America, the most commonly occurring mutation is known as A4V and occurs in up to 50% of SOD1 cases. In people of ]n extraction there is a relatively benign mutation called D90A which is associated with a slow progression. Future research is concentrating on identifying new genetic mutations and the clinical syndrome associated with them. Familial MND may also confer a higher risk of developing cognitive changes such as frontotemporal dementia or executive dysfunction (see 'extra-motor change in MND' below).


] (TDP-43), is a critical component of the ] (NHEJ) enzymatic pathway that ] ] in pluripotent ]-derived motor neurons.<ref name =Mitra2019>{{cite journal | vauthors = Mitra J, Guerrero EN, Hegde PM, Liachko NF, Wang H, Vasquez V, Gao J, Pandey A, Taylor JP, Kraemer BC, Wu P, Boldogh I, Garruto RM, Mitra S, Rao KS, Hegde ML | display-authors = 6 | title = Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 10 | pages = 4696–4705 | date = March 2019 | pmid = 30770445 | pmc = 6410842 | doi = 10.1073/pnas.1818415116 | bibcode = 2019PNAS..116.4696M | doi-access = free }}</ref> TDP-43 is rapidly recruited to double-strand breaks where it acts as a scaffold for the recruitment of the ]-] protein complex that then acts to repair double-strand breaks. About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal motor neurons of TDP43. In TDP-43 depleted human neural stem cell-derived motor neurons, as well as in sporadic ] patients' spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ.<ref name=Mitra2019/>
It is thought that ''SOD1'' mutations confer a toxic gain, rather than a loss, of function to the enzyme. SOD1 mutations may increase the propensity for the enzyme to form protein aggregates which are toxic to nerve cells.


=== Associated risk factors ===
===Pathophysiology===
In adults, men are more commonly affected than women.<ref name="NINDS2014" />
]s are innervated by a group of neurones (''lower motor neurones'') located in the ventral horns of the spinal cord which project out the ventral roots to the muscle cells. These nerve cells are themselves innervated by the corticospinal tract or ''upper motor neurones'' that project from the ] of the brain. On macroscopic pathology, there is a degeneration of the ventral horns of the spinal cord, as well as atrophy of the ventral roots. In the brain, atrophy may be present in the frontal and temporal lobes. On microscopic examination, neurones may show spongiosis, the presence of astrocytes, and a number of inclusions including characteristic "skein-like" inclusions, bunina bodies, and vacuolisation.


== Diagnosis ==
There is a role in excitotoxicity and oxidative stress, presumably secondary to mitochondrial dysfunction. In animal models, death by ] has also been identified.
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 ===
==Emotional lability / pseudobulbar affect==
]
{{main|labile affect}}
Motor neuron disease describes a collection of clinical disorders, characterized by progressive muscle weakness and the degeneration of the motor neuron on ]. 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" />
Around a third of all MND patients experience ], also known as emotional lability, pseudobulbar affect, or pathological laughter and crying. Patients with pseudobulbar palsy are particularly likely to be affected, as are patients with PLS.


# Is the disease sporadic or inherited?
==Extra-motor change in MND==
# Is there involvement of the ]s (UMN), the ]s (LMN), or both?
] change can and does occur in between 33&ndash;50% of patients. A small proportion exhibit a form of ] characterised by behavioural abnormalities such as ], ], and personality changes. A small proportion of patients may also suffer from an ], which causes difficulty in naming specific objects. A larger proportion (up to 50%) suffer from a milder version of cognitive change which primarily affects what is known as ]. Briefly, this is the ability of an individual to initiate, inhibit, sustain, and switch attention and is involved in the organisation of complex tasks down to smaller components. Often patients with such changes find themselves unable to do the family finances or drive a car. ] is surprisingly rare in MND (around 5&ndash;20%) relative to the frequency with which it is found in other, less severe, neurological disorders e.g. ~50% in ] and ], ~20% in Epilepsy. Depression does not necessarily increase as the symptoms progress, and in fact many patients report being happy with their ] despite profound disability. This may reflect the use of ] such as reevaluating what is important in life.


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: ], ], or ]. 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" />
Although traditionally thought only to affect the motor system, sensory abnormalities are not necessarily absent, with some patients finding altered sensation to touch and heat, found in around 10% of patients. Patients with a predominantly upper motor neurone syndrome, and particularly PLS, often report an enhanced startle reflex to loud noises.


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>
Neuroimaging and neuropathology has demonstrated extra-motor changes in the frontal lobes including the inferior frontal gyrus, superior frontal gyrus, anterior cingulate cortex, and superior temporal gyrus. The degree of pathology in these areas has been directly related to the degree of cognitive change experienced by the patient, if any. Patients with MND and dementia have been shown to exhibit marked frontotemporal lobe atrophy as revealed by ] or ] ].


{| class="wikitable"
==Epidemiology==
! Type !! UMN degeneration !! LMN degeneration
The incidence of MND is approximately 1&ndash;5 out of 100,000 people. Men have a slightly higher incidence rate than women. Approximately 5,600 cases are diagnosed in the U.S. every year. By far the greatest risk factor is age, with symptoms typically presenting between the ages of 50-70. Cases under the age of 50 years are called "young onset MND", whilst incidence rates appear to tail off after the age of 85.
|-
| 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, ] 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 ===
Tentative environmental risk factors identified so far include: exposure to severe electrical shock leading to coma, having served in the first ], and playing professional ]. However, these findings have not been firmly identified and more research is needed.
* ] (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>
* ] (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" />
* ] (EMG) & ] (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 ] 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 ] (CMAP), which results from the loss of motor neurons, but the ]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>
* ]: 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.


== Treatment ==
There are three "hot spots" of MND in the world. One is in the Kii peninsula of Japan, one amongst a tribal population in ]. Until the 1960s, Chamorro inhabitants from the island of ] in the ] had an increased risk of developing a form of MND known as Guamanian ALS-PD-dementia complex or "lytico bodig", but since then the incidence rates have returned to near normal, and nobody born since 1940 has developed the disease. Putative theories involve neurotoxins in local wildlife including ] nuts and other traditional foodstuffs.
There are no known curative treatments for the majority of motor neuron disorders. Please refer to the articles on individual disorders for more details.<ref>{{Cite web|url=https://www.ninds.nih.gov/Disorders/All-Disorders/Motor-Neuron-Diseases-Information-Page|title=NIH: ninds: Motor Neuron Diseases Information Page|date=27 March 2019|access-date=18 November 2019}}</ref>


==Treatment== == Prognosis ==
The table below lists life expectancy for patients who are diagnosed with MND.
Currently there is no cure for ALS. The only drug that affects the course of the disease is ]. The drug functions by blocking the effects of the neurotransmitter glutamate, and is thought to extend the lifespan of an ALS patient by only a few months.
{| class="wikitable"
!Type
!Median survival time <br />from start of symptoms
|-
|Amyotrophic lateral sclerosis (ALS)
|2–5 years<ref name=":12" /><ref name=":10">{{cite web |url=https://imnda.ie/about-mnd/different-types-of-mnd/ |title=Different types of MND | work = Irish Motor Neurone Disease Association |access-date=2018-12-12}}</ref>
|-
|Primary lateral sclerosis (PLS)
|8–10 years<ref name=":12" />
|-
|Progressive muscular atrophy (PMA)
|2–4 years<ref name=":12" />
|-
|Progressive bulbar palsy (PBP)
|6 months – 3 years<ref name=":10" />
|-
|Pseudobulbar palsy
|No change in survival
|}


==Terminology==
The lack of effective medications to slow the progression of ALS does not mean that patients with ALS cannot be medically cared for. Instead, treatment of patients with ALS focuses on the relief of symptoms associated with the disease. This involves a variety of health professionals including neurologists, physical therapists, occupational therapists, dieticians, respiratory therapists, social workers, palliative care specialists, specialist nurses and psychologists. A list of neurology clinics that specialize in the care of patients with ALS can be found on the World Federation of Neurology website (http://www.wfnals.org/clinics/).
In the United States and Canada, the term ''motor neuron disease'' usually refers to the group of disorders while amyotrophic lateral sclerosis is frequently called ''Lou Gehrig's disease''.<ref name=NINDS2014/><ref name=":14">{{Cite book |title=Clinical and molecular aspects of motor neuron disease | vauthors = Cooper-Knock J, Jenkins T, Shaw PJ |isbn=978-1-61504-429-0|location=San Rafael, California |oclc=860981760|date = 2013-09-01}}</ref><ref name=":3">{{cite journal | vauthors = Shaw PJ | title = Molecular and cellular pathways of neurodegeneration in motor neurone disease | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 76 | issue = 8 | pages = 1046–1057 | date = August 2005 | pmid = 16024877 | pmc = 1739758 | doi = 10.1136/jnnp.2004.048652 | quote = Many doctors use the terms motor neuron disease and ALS interchangeably. }}</ref> In the United Kingdom and Australia, the term ''motor neuron(e) disease'' is used for amyotrophic lateral sclerosis,<ref name="NHS"/><ref name="healthdirectAU"/> although is not uncommon to refer to the entire group.<ref name=":15">{{cite web |url=https://www.mndassociation.org/wp-content/uploads/2015/02/an-introduction-to-mnd-booklet.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://www.mndassociation.org/wp-content/uploads/2015/02/an-introduction-to-mnd-booklet.pdf |archive-date=2022-10-09 |url-status=live|title=An introduction to motor neurone disease (MND) |website=motor neurone disease association|date= 2015}}</ref><ref>{{Cite book |title=Neurodegeneration| vauthors = Schapira AH, Wszolek ZK, Dawson TM, Wood NW |isbn=978-1-118-66191-8 |location=Chichester, West Sussex |oclc=958876527 | date = 2017-02-13 }}</ref>


While MND refers to a specific subset of similar diseases, there are numerous other diseases of ]s that are referred to collectively as "motor neuron disorders", for instance the diseases belonging to the ] group.<ref name=El2008>{{cite book | vauthors = Ince PG, Clark B, Holton J, Revesz T, Wharton SB | chapter = Chapter 13: Diseases of movement and system degenerations | veditors = Greenfield JG, Love S, Louis DN, Ellison DW |title=Greenfield's neuropathology|date=2008|publisher=Hodder Arnold|location=London|isbn=978-0-340-90681-1 | volume = 1 |page=947|edition=8th|chapter-url=https://books.google.com/books?id=nrEWkAc7W7IC&pg=PA947}}</ref> However, they are not classified as "motor neuron diseases" by the 11th edition of the ] (ICD-11),<ref>{{Cite web|url=https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f661720689|title=8B60 Motor neuron disease|website=ICD-11 for Mortality and Morbidity Statistics|publisher=World Health Organisation}}</ref> which is the definition followed in this article.
==Research efforts==
The search for a drug that will slow MND progression is underway. For example, recent research using mouse models suggests that ], a common antibiotic, may also be effective in extending the lifespan of MND sufferers. This drug must pass ] with ALS patients before it may be used as a general treatment for MND.


== See also ==
] extends the lifespan of MND mice with SOD1 mutations, but it does not prevent their eventual death. Other agents that are currently in trials include ], ], ] and ] to name but a few. A list of US-based clinical MND trials may be found at www.clinicaltrials.org or by contacting your local ALS/MND charity.
* ]
* ]


==Etymology== == References ==
{{reflist}}
''Amyotrophic'' comes from the ]: ''A-'' means "no", ''myo'' refers to "muscle", and ''trophic'' means "nourishment"; ''amyotrophic'' therefore means "no muscle nourishment," which describes the characteristic ] of the sufferer's disused muscle tissue. ''Lateral'' identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("]") in the region


== External links ==
==History and prominent patients==
* {{Commons-inline}}
] baseball player ] brought national and international attention to the disease in ] when he abruptly retired after being diagnosed with ALS/MND; he would die two years later. Former guitar virtuoso ] and ] ] also suffer from the disease.
* {{NINDS|Motor-Neuron-Diseases|Motor neuron diseases}}

{{Medical resources
Founder of care homes ] VC, owner from 1957-1966 of ] House in Dorset Sir Robert Cooke F.R.C.S., ] ], ] ]er ], ] ] ], ] singer and guitarist ], ] Chairman ], ] giant ], ] actor ], legendary ] manager ], teacher and book subject ], American television actor ], linguist ], '']'' journalist ], avant-garde guitarist ], American ] veteran ], libertarian writer, politician, and investment analyst, ], and ex-] ] player ] died from the disease.
| DiseasesDB = 8358

| ICD11 = {{ICD11|8B60}}
] was a British woman with the disease who was involved in a prominent ] case in the early ].
| ICD10 = {{ICD10|G12.2}}

| ICD9 = {{ICD9|335.2}}
==See also==
| ICDO =
* ]
| OMIM =
* ]
| MedlinePlus =
* ]
| eMedicineSubj =
* ]
| eMedicineTopic =
* ]
| MeshID = D016472

}}
==Sources and references==
{{CNS diseases of the nervous system}}
*
:Motor Neuron Diseases information sheet compiled by the National Institute of Neurological Disorders and Stroke (NINDS).
*
* Some information gathered from Dr. M Norenberg, ] (] ]).
* ''Crossing the Finishing Line&mdash;Last Thoughts of Leonard Cheshire VC'', ed. ] (London 1998).
* '']'' (] newspaper), ] ].
* Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu du C, Gullans S, Ferrante RJ, Przedborski S, Kristal BS, Friedlander RM. "Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice." Nature. 2002 ];417(6884):74-8.
* Van Den Bosch L, Tilkin P, Lemmens G, Robberecht W. "Minocycline delays disease onset and mortality in a transgenic model of ALS." Neuroreport. 2002 ];13(8):1067-70.
* Kriz J, Nguyen MD, Julien JP. "Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis." Neurobiol Dis. 2002 Aug;10(3):268-78.

==Information about clinical trials==
*
*
*] players to MND]

==Other resources==
*
*
*
*
*
* - Australian group seeking to find a cure for familial Motor Neurone Disease.
*
*
*
*
*
* {{GPnotebook|644546567}}

]
]
]


{{DEFAULTSORT:Motor neuron disease}}
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Latest revision as of 22:21, 9 July 2024

Group of neurological disorders affecting motor neurons This article is about a group of muscle-wasting disorders. For the disease amyotrophic lateral sclerosis, also known as motor neuron(e) disease, see Amyotrophic lateral sclerosis.

Medical condition
Motor neuron disease
spinal diagram
SpecialtyNeurology

Motor neuron diseases or motor neurone diseases (MNDs) are a group of rare neurodegenerative disorders that selectively affect motor neurons, the cells which control voluntary muscles of the body. They include amyotrophic lateral sclerosis (ALS), progressive bulbar palsy (PBP), pseudobulbar palsy, progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), spinal muscular atrophy (SMA) and monomelic amyotrophy (MMA), as well as some rarer variants resembling ALS.

Motor neuron diseases affect both children and adults. While each motor neuron disease affects patients differently, they all cause movement-related symptoms, mainly muscle weakness. Most of these diseases seem to occur randomly without known causes, but some forms are inherited. Studies into these inherited forms have led to discoveries of various genes (e.g. SOD1) that are thought to be important in understanding how the disease occurs.

Symptoms of motor neuron diseases can be first seen at birth or can come on slowly later in life. Most of these diseases worsen over time; while some, such as ALS, shorten one's life expectancy, others do not. Currently, there are no approved treatments for the majority of motor neuron disorders, and care is mostly symptomatic.

Signs and symptoms

A man with amyotrophic lateral sclerosis (ALS). (A) He needs assistance to stand. (B) Advanced atrophy of the tongue. (C) There is upper limb and truncal muscle atrophy with a positive Babinski sign. (D) Advanced thenar muscle atrophy.

Signs and symptoms depend on the specific disease, but motor neuron diseases typically manifest as a group of movement-related symptoms. They come on slowly, and worsen over the course of more than three months. Various patterns of muscle weakness are seen, and muscle cramps and spasms may occur. One can have difficulty breathing with climbing stairs (exertion), difficulty breathing when lying down (orthopnea), or even respiratory failure if breathing muscles become involved. Bulbar symptoms, including difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and excessive saliva production (sialorrhea), can also occur. Sensation, or the ability to feel, is typically not affected. Emotional disturbance (e.g. pseudobulbar affect) and cognitive and behavioural changes (e.g. problems in word fluency, decision-making, and memory) are also seen. There can be lower motor neuron findings (e.g. muscle wasting, muscle twitching), upper motor neuron findings (e.g. brisk reflexes, Babinski reflex, Hoffman's reflex, increased muscle tone), or both.

Motor neuron diseases are seen both in children and adults. Those that affect children tend to be inherited or familial, and their symptoms are either present at birth or appear before learning to walk. Those that affect adults tend to appear after age 40. The clinical course depends on the specific disease, but most progress or worsen over the course of months. Some are fatal (e.g. ALS), while others are not (e.g. PLS).

Patterns of weakness

Various patterns of muscle weakness occur in different motor neuron diseases. Weakness can be symmetric or asymmetric, and it can occur in body parts that are distal, proximal, or both. According to Statland et al., there are three main weakness patterns that are seen in motor neuron diseases, which are:

  1. Asymmetric distal weakness without sensory loss (e.g. ALS, PLS, PMA, MMA)
  2. Symmetric weakness without sensory loss (e.g. PMA, PLS)
  3. Symmetric focal midline proximal weakness (neck, trunk, bulbar involvement; e.g. ALS, PBP, PLS)

Lower and upper motor neuron findings

Motor neuron diseases are on a spectrum in terms of upper and lower motor neuron involvement. Some have just lower or upper motor neuron findings, while others have a mix of both. Lower motor neuron (LMN) findings include muscle atrophy and fasciculations, and upper motor neuron (UMN) findings include hyperreflexia, spasticity, muscle spasm, and abnormal reflexes.

Pure upper motor neuron diseases, or those with just UMN findings, include PLS.

Pure lower motor neuron diseases, or those with just LMN findings, include PMA.

Motor neuron diseases with both UMN and LMN findings include both familial and sporadic ALS.

Causes

Most cases are sporadic and their causes are usually not known. It is thought that environmental, toxic, viral, or genetic factors may be involved.

DNA damage

TAR DNA-binding protein 43 (TDP-43), is a critical component of the non-homologous end joining (NHEJ) enzymatic pathway that repairs DNA double-strand breaks in pluripotent stem cell-derived motor neurons. TDP-43 is rapidly recruited to double-strand breaks where it acts as a scaffold for the recruitment of the XRCC4-DNA ligase protein complex that then acts to repair double-strand breaks. About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal motor neurons of TDP43. In TDP-43 depleted human neural stem cell-derived motor neurons, as well as in sporadic ALS patients' spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ.

Associated risk factors

In adults, men are more commonly affected than women.

Diagnosis

Differential diagnosis can be challenging due to the number of overlapping symptoms, shared between several motor neuron diseases. 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.

Classification

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 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.

All types of MND can be differentiated by two defining characteristics:

  1. Is the disease sporadic or inherited?
  2. Is there involvement of the upper motor neurons (UMN), the lower motor neurons (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, 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.

UMNs are motor neurons that project from the cortex down to the brainstem or spinal cord. LMNs originate in the anterior horns of the spinal cord and synapse on peripheral muscles. 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.

Type UMN degeneration LMN degeneration
Sporadic MNDs
Sporadic amyotrophic lateral sclerosis (ALS)* Yes Yes
Primary lateral sclerosis (PLS)* Yes No
Progressive muscular atrophy (PMA)* No Yes
Progressive bulbar palsy (PBP)* Yes Yes, bulbar region
Pseudobulbar palsy Yes, bulbar region No
Monomelic amyotrophy (MMA) No Yes
Inherited MNDs
Familial amyotrophic lateral sclerosis (ALS)* Yes Yes

Tests

  • Cerebrospinal fluid (CSF) tests: Analysis of the fluid from around the brain and spinal cord could reveal signs of an infection or inflammation.
  • 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).
  • 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.
  • 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 neurons should remain unaffected.
  • 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.

Treatment

There are no known curative treatments for the majority of motor neuron disorders. Please refer to the articles on individual disorders for more details.

Prognosis

The table below lists life expectancy for patients who are diagnosed with MND.

Type Median survival time
from start of symptoms
Amyotrophic lateral sclerosis (ALS) 2–5 years
Primary lateral sclerosis (PLS) 8–10 years
Progressive muscular atrophy (PMA) 2–4 years
Progressive bulbar palsy (PBP) 6 months – 3 years
Pseudobulbar palsy No change in survival

Terminology

In the United States and Canada, the term motor neuron disease usually refers to the group of disorders while amyotrophic lateral sclerosis is frequently called Lou Gehrig's disease. In the United Kingdom and Australia, the term motor neuron(e) disease is used for amyotrophic lateral sclerosis, although is not uncommon to refer to the entire group.

While MND refers to a specific subset of similar diseases, there are numerous other diseases of motor neurons that are referred to collectively as "motor neuron disorders", for instance the diseases belonging to the spinal muscular atrophies group. However, they are not classified as "motor neuron diseases" by the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), which is the definition followed in this article.

See also

References

  1. ^ Ince PG, Clark B, Holton J, Revesz T, Wharton SB (2008). "Chapter 13: Diseases of movement and system degenerations". In Greenfield JG, Love S, Louis DN, Ellison DW (eds.). Greenfield's neuropathology. Vol. 1 (8th ed.). London: Hodder Arnold. p. 947. ISBN 978-0-340-90681-1.
  2. ^ "Motor Neuron Diseases Fact Sheet: National Institute of Neurological Disorders and Stroke (NINDS)". ninds.nih.gov. Archived from the original on 13 April 2014. Retrieved 7 November 2010.
  3. ^ "Motor neurone disease – NHS". nhs.uk. 15 January 2018. Retrieved 24 October 2020.
  4. ^ Healthdirect Australia (17 April 2020). "Motor neurone disease (MND)". healthdirect.gov.au. Retrieved 24 October 2020.
  5. ^ Cooper-Knock J, Jenkins T, Shaw PJ (1 September 2013). Clinical and molecular aspects of motor neuron disease. San Rafael, California. ISBN 978-1-61504-429-0. OCLC 860981760.{{cite book}}: CS1 maint: location missing publisher (link)
  6. ^ Statland JM, Barohn RJ, McVey AL, Katz JS, Dimachkie MM (November 2015). "Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis". Neurologic Clinics. 33 (4): 735–748. doi:10.1016/j.ncl.2015.07.006. PMC 4629510. PMID 26515618.
  7. Cooper-Knock J, Jenkins T, Shaw PJ (1 September 2013). Clinical and molecular aspects of motor neuron disease. San Rafael, California (1537 Fourth Street, San Rafael, CA 94901 USA). ISBN 9781615044290. OCLC 860981760.{{cite book}}: CS1 maint: location (link) CS1 maint: location missing publisher (link)
  8. "Patient with amyotrophic lateral sclerosis (ALS) (case | Open-i". openi.nlm.nih.gov. Archived from the original on 15 December 2018. Retrieved 12 December 2018.
  9. Barohn RJ, Amato AA (May 2013). "Pattern-recognition approach to neuropathy and neuronopathy". Neurologic Clinics. 31 (2): 343–361. doi:10.1016/j.ncl.2013.02.001. PMC 3922643. PMID 23642713.
  10. Emos MC, Agarwal S (2022). "Neuroanatomy, Upper Motor Neuron Lesion". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30725990. Retrieved 24 June 2022.
  11. "Progressive Muscular Atrophy – an overview | ScienceDirect Topics". sciencedirect.com. Retrieved 24 June 2022.
  12. "Motor Neuron Diseases Fact Sheet | National Institute of Neurological Disorders and Stroke". ninds.nih.gov. Retrieved 24 June 2022.
  13. ^ Mitra J, Guerrero EN, Hegde PM, Liachko NF, Wang H, Vasquez V, et al. (March 2019). "Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects". Proceedings of the National Academy of Sciences of the United States of America. 116 (10): 4696–4705. Bibcode:2019PNAS..116.4696M. doi:10.1073/pnas.1818415116. PMC 6410842. PMID 30770445.
  14. Statland, Jeffrey M.; Barohn, Richard J.; McVey, April L.; Katz, Jonathan; Dimachkie, Mazen M. (2015). "Patterns of Weakness, Classification of Motor Neuron Disease & Clinical Diagnosis of Sporadic ALS". Neurologic Clinics. 33 (4): 735–748. doi:10.1016/j.ncl.2015.07.006. ISSN 0733-8619. PMC 4629510. PMID 26515618.
  15. "Archive | Practical Neurology". pn.bmj.com. Retrieved 24 June 2022.
  16. ^ Foster LA, Salajegheh MK (January 2019). "Motor Neuron Disease: Pathophysiology, Diagnosis, and Management". The American Journal of Medicine. 132 (1): 32–37. doi:10.1016/j.amjmed.2018.07.012. PMID 30075105. S2CID 51910723.
  17. ^ "What forms does MND take?". mndnsw.asn.au. Retrieved 11 December 2018.
  18. ^ Blumenfeld H (2002). Neuroanatomy through clinical cases. Sunderland, Mass.: Sinauer. ISBN 087893060-4. OCLC 44628054.
  19. Javed K, Daly DT (2022). "Neuroanatomy, Lower Motor Neuron Lesion". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30969636. Retrieved 24 June 2022.
  20. Duleep A, Shefner J (February 2013). "Electrodiagnosis of motor neuron disease". Physical Medicine and Rehabilitation Clinics of North America. 24 (1): 139–151. doi:10.1016/j.pmr.2012.08.022. PMID 23177036.
  21. "NIH: ninds: Motor Neuron Diseases Information Page". 27 March 2019. Retrieved 18 November 2019.
  22. ^ "Different types of MND". Irish Motor Neurone Disease Association. Retrieved 12 December 2018.
  23. Shaw PJ (August 2005). "Molecular and cellular pathways of neurodegeneration in motor neurone disease". Journal of Neurology, Neurosurgery, and Psychiatry. 76 (8): 1046–1057. doi:10.1136/jnnp.2004.048652. PMC 1739758. PMID 16024877. Many doctors use the terms motor neuron disease and ALS interchangeably.
  24. "An introduction to motor neurone disease (MND)" (PDF). motor neurone disease association. 2015. Archived (PDF) from the original on 9 October 2022.
  25. Schapira AH, Wszolek ZK, Dawson TM, Wood NW (13 February 2017). Neurodegeneration. Chichester, West Sussex. ISBN 978-1-118-66191-8. OCLC 958876527.{{cite book}}: CS1 maint: location missing publisher (link)
  26. "8B60 Motor neuron disease". ICD-11 for Mortality and Morbidity Statistics. World Health Organisation.

External links

ClassificationD
Diseases of the nervous system, primarily CNS
Inflammation
Brain
Brain and spinal cord
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
Dementia

Creutzfeldt–Jakob disease

Mitochondrial disease
Demyelinating
Episodic/
paroxysmal
Seizures and epilepsy
Headache
Cerebrovascular
Other
CSF
Other
Both/either
Degenerative
SA
MND
Categories: