Progressive muscular atrophy
Encyclopedia
Progressive muscular atrophy (PMA) is a rare subtype of amyotrophic lateral sclerosis
(ALS) or motor neurone disease
(MND) which affects only the lower motor neurones. PMA is thought to account for around 4% of all ALS/MND cases. This is in contrast to the most common form of ALS/MND, amyotrophic lateral sclerosis
, which affects both the upper and lower motor neurones, or another rare form of ALS/MND, primary lateral sclerosis
, which affects only the upper motor neurones. The distinction is important because PMA is associated with a better prognosis than classical ALS/MND.
Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as "Flail Arm" (FA) or "Flail Leg" (FL) and are associated with a better prognosis.
or primary lateral sclerosis
, PMA is distinguished by the absence of:
, there is no specific test which can conclusively establish whether a patient has the condition. Instead, a number of other possibilities have to be ruled out, such as multifocal motor neuropathy
or spinal muscular atrophy
. Tests used in the diagnostic process include MRI, clinical examination
, and EMG
. EMG tests in patients who do have PMA usually show denervation (neurone death) in most affected body parts, and in some unaffected parts too.
It typically takes longer to be diagnosed with PMA than ALS/MND, an average of 20 months for PMA vs 15 months in ALS/MND.
An initial diagnosis of PMA could turn out to be slowly progressive ALS/MND many years later, sometimes even decades after the initial diagnosis. The occurrence of upper motor neurone symptoms such as brisk reflexes, spasticity, or a Babinski sign would indicate a progression to ALS/MND; the correct diagnosis is also occasionally made on autopsy.
over whether PMA is a distinct disease with its own characteristics, or if lies somewhere on a spectrum with ALS/MND, PLS, and PBP. Charcot, who first described ALS/MND in 1870, felt the PMA was a separate condition, with degeneration of the lower motor neurones the most important lesion, whereas in ALS it was the upper motor neurone degeneration that was primary, with lower motor neurone degeneration being secondary. Such views still exist in archaic terms for PMA such as "Primary progressive spinal muscular atrophy". Throughout the course of the late 19th century, other conditions were discovered which had previously been thought to be PMA, such as pseudo-hypertrophic paralysis, hereditary muscular atrophy, progressive myopathy, progressive muscular dystrophy
, peripheral neuritis, and syringomyelia.
The neurologists Dejerine and Gowers were among those who felt PMA was part of a spectrum of "motor neurone disease" including ALS, PMA, and PBP, in part because it was almost impossible to distinguish the conditions at autopsy. Other researchers have suggested that PMA is just ALS/MND in an earlier stage of progression, because although the upper motor neurones appear unaffected on clinical examination there are in fact detectable pathological signs of upper motor neurone damage on autopsy.
In favour of considering PMA a separate disease, some patients with PMA live for decades after diagnosis, which would be unusual in typical ALS/MND.
To this day, terminology around these diseases remains confusing because in the UK "((motor neurone disease))" refers to both ALS specifically and to the spectrum of ALS, PMA, PLS, and PBP. In the United States the most common terms are ALS (both specifically for ALS and as a blanket term) or "Lou Gehrig's disease".
- Former British Lions
rugby captain and head coach
at Wigan rugby club
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
(ALS) or motor neurone disease
Motor neurone disease
The motor neurone diseases are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body. They are generally progressive in nature, and can cause...
(MND) which affects only the lower motor neurones. PMA is thought to account for around 4% of all ALS/MND cases. This is in contrast to the most common form of ALS/MND, amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
, which affects both the upper and lower motor neurones, or another rare form of ALS/MND, primary lateral sclerosis
Primary lateral sclerosis
Primary lateral sclerosis is a rare neuromuscular disease characterized by progressive muscle weakness in the voluntary muscles. PLS belongs to a group of disorders known as motor neuron diseases...
, which affects only the upper motor neurones. The distinction is important because PMA is associated with a better prognosis than classical ALS/MND.
History
Despite being rarer than ALS/MND, PMA was actually described earlier, when in 1850 French Neurologist Francois Aran described 11 cases which he termed atrophie musculaire progressive. Contemporary neurologist Duchenne also claimed to have described the condition one year earlier, but the written report was never found; an archaic term for the disease was once "Aran-Duchenne disease" or "Duchenne-Aran disease".Symptoms
As a result of lower motor neurone degeneration, the symptoms of PMA include:- atrophyAtrophyAtrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
- fasciculationFasciculationA fasciculation , or "muscle twitch", is a small, local, involuntary muscle contraction and relaxation visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers...
s - muscle weaknessMuscle weaknessMuscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as "Flail Arm" (FA) or "Flail Leg" (FL) and are associated with a better prognosis.
Differential diagnosis
In contrast to amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
or primary lateral sclerosis
Primary lateral sclerosis
Primary lateral sclerosis is a rare neuromuscular disease characterized by progressive muscle weakness in the voluntary muscles. PLS belongs to a group of disorders known as motor neuron diseases...
, PMA is distinguished by the absence of:
- brisk reflexes
- spasticitySpasticitySpasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
- Babinski's sign
- Emotional lability
Diagnosis
PMA is a diagnosis of exclusionDiagnosis of exclusion
A diagnosis of exclusion is a medical condition reached by a process of elimination, which may be necessary if presence cannot be established with complete confidence from examination or testing...
, there is no specific test which can conclusively establish whether a patient has the condition. Instead, a number of other possibilities have to be ruled out, such as multifocal motor neuropathy
Multifocal motor neuropathy
Multifocal motor neuropathy is a progressively worsening condition where muscles in the extremities gradually weaken. The disorder, a pure motor neuropathy syndrome, is sometimes mistaken for amyotrophic lateral sclerosis because of the similarity in the clinical picture, especially if muscle...
or spinal muscular atrophy
Spinal muscular atrophy
Spinal Muscular Atrophy is a neuromuscular disease characterized by degeneration of motor neurons, resulting in progressive muscular atrophy and weakness. The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness...
. Tests used in the diagnostic process include MRI, clinical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
, and EMG
Electromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
. EMG tests in patients who do have PMA usually show denervation (neurone death) in most affected body parts, and in some unaffected parts too.
It typically takes longer to be diagnosed with PMA than ALS/MND, an average of 20 months for PMA vs 15 months in ALS/MND.
Prognosis
The importance of correctly recognizing progressive muscular atrophy as opposed to ALS/MND is important for several reasons.- 1) the prognosis is a little better. A recent study found the 5-year survival rateSurvival rateIn biostatistics, survival rate is a part of survival analysis, indicating the percentage of people in a study or treatment group who are alive for a given period of time after diagnosis...
in PMA to be 33% (vs 20% in ALS/MND) and the 10-year survival rate to be 12% (vs 6% in ALS/MND). - 2) Patients with PMA do not suffer from the cognitive change identified in at least a subgroup of patients with ALS.
- 3) Because PMA patients don’t have UMN signs, they usually do not meet the "World Federation of Neurology El EscorialEl EscorialThe Royal Seat of San Lorenzo de El Escorial is a historical residence of the king of Spain, in the town of San Lorenzo de El Escorial, about 45 kilometres northwest of the capital, Madrid, in Spain. It is one of the Spanish royal sites and functions as a monastery, royal palace, museum, and...
Research Criteria" for “Definite” or “Probable” ALS/MND and so are ineligible to participate in the majority of clinical researchClinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
trials such as drugs trials or brain scans. - 4) Because of its rarity (even compared to ALS/MND) and confusion about the condition, some insurance policiesInsurance contractIn insurance, the insurance policy is a contract between the insurer and the insured, known as the policyholder, which determines the claims which the insurer is legally required to pay. In exchange for payment, known as the premium, the insurer pays for damages to the insured which are caused by...
or local healthcare policies may not recognize PMA as being the life-changing illness that it is. In cases where being classified as being PMA rather than ALS/MND is likely to restrict access to services, it may be preferable to be diagnosed as "slowly progressive ALS/MND" or "lower motor neuronMotor neuronIn vertebrates, the term motor neuron classically applies to neurons located in the central nervous system that project their axons outside the CNS and directly or indirectly control muscles...
e predominant" ALS/MND.
An initial diagnosis of PMA could turn out to be slowly progressive ALS/MND many years later, sometimes even decades after the initial diagnosis. The occurrence of upper motor neurone symptoms such as brisk reflexes, spasticity, or a Babinski sign would indicate a progression to ALS/MND; the correct diagnosis is also occasionally made on autopsy.
Disease or syndrome?
Since its initial description in 1850, there has been debate in the scientific literatureScientific literature
Scientific literature comprises scientific publications that report original empirical and theoretical work in the natural and social sciences, and within a scientific field is often abbreviated as the literature. Academic publishing is the process of placing the results of one's research into the...
over whether PMA is a distinct disease with its own characteristics, or if lies somewhere on a spectrum with ALS/MND, PLS, and PBP. Charcot, who first described ALS/MND in 1870, felt the PMA was a separate condition, with degeneration of the lower motor neurones the most important lesion, whereas in ALS it was the upper motor neurone degeneration that was primary, with lower motor neurone degeneration being secondary. Such views still exist in archaic terms for PMA such as "Primary progressive spinal muscular atrophy". Throughout the course of the late 19th century, other conditions were discovered which had previously been thought to be PMA, such as pseudo-hypertrophic paralysis, hereditary muscular atrophy, progressive myopathy, progressive muscular dystrophy
Muscular dystrophy
Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...
, peripheral neuritis, and syringomyelia.
The neurologists Dejerine and Gowers were among those who felt PMA was part of a spectrum of "motor neurone disease" including ALS, PMA, and PBP, in part because it was almost impossible to distinguish the conditions at autopsy. Other researchers have suggested that PMA is just ALS/MND in an earlier stage of progression, because although the upper motor neurones appear unaffected on clinical examination there are in fact detectable pathological signs of upper motor neurone damage on autopsy.
In favour of considering PMA a separate disease, some patients with PMA live for decades after diagnosis, which would be unusual in typical ALS/MND.
To this day, terminology around these diseases remains confusing because in the UK "((motor neurone disease))" refers to both ALS specifically and to the spectrum of ALS, PMA, PLS, and PBP. In the United States the most common terms are ALS (both specifically for ALS and as a blanket term) or "Lou Gehrig's disease".
Notable people with PMA
Mike GregoryMike Gregory
Michael Keith "Mike" Gregory , was a rugby league player and later coach; the former head coach of Wigan and player for Warrington and Great Britain.-Playing career:...
- Former British Lions
British and Irish Lions
The British and Irish Lions is a rugby union team made up of players from England, Scotland, Ireland and Wales...
rugby captain and head coach
Head coach
A head coach, senior coach or manager is a professional at training and developing athletes. They typically hold a more public profile and are paid more than other coaches...
at Wigan rugby club