I was reading back the post on ‘HNPP and Pain’ , when I came across this statement, “But with HNPP, which causes demyelination…”, and it got me thinking about demyelination and the presentation of HNPP. And, alas, the poor state of my english grammar… ahem… but onward… this entry is published but incomplete…
Just how does demyelination actually occur in HNPP?
I’m not sure that anyone truly knows the answer to this, however, in HNPP it is primarily to do with the deficiency of Peripheral Myelin Protein (PMP22 – What does the 22 stand for?). The exact function of PMP22 is unknown, it is found primarily in the sensory-motor peripheral nervous system, that is the part of the peripheral nervous system that controls our skeletal muscles along with the senses of touch, vibration, position, touch-temperature. It is sometimes referred to as the ‘voluntary nervous system’, the muscles that we have control over, another name is the somatic nervous system.
Although PMP22 occurs in other body tissues, it is the peripheral nervous system that is particularly sensitive to changes in the PMP22 gene. CMT1a and HNPP do not cause (on the whole) this protein to be mutated, but because of the duplication (CMT1a) and the deletion (HNPP) of a region of chromosome 17, these diseases cause a change in ‘Gene Dosage‘.
So why does this cause demyelination?
I suppose the answer to this is still unknown, but it has been observed that peripheral nerves are very sensitive to the number of copies of this gene. Two copies are needed for ideal peripheral nerve function. Having only one copy causes the myelin to become more fragile, making it more suseptible to injury, HNPP. Three copies of the gene causes HNPP’s genetic opposite, CMT1a, which is also known to cause demyelination, which appears to be more steadily progressive than HNPP. CMT1a is generally thought to be a more severe generalised polyneuropathy, mostly affecting the longer nerves first and gradually traveling toward the centre of the body, distal toward proximal ( At a distance moving toward, ‘in the proximity of’ , the centre) .
HNPP also has an underlying gradually progressive polyneuropathy, which can be shown by nerve conduction studies. HNPP affects the speed of the nerve impulse, and delays the impulse. Conduction velocities of a group of large fibre peripheral nerves is in the region of 30- 40 m/s. This is somewhat lower than would normally be expected, but on it’s own would unlikely cause prominent symptoms. Many neurologists have called this ‘borderline’, on the low end of the scale, that would not be expected to cause symptoms or elicit signs of neuropathy. These results would only be expected if a pressure palsy or nerve compression was not active. In that case there would be discontinuities in the nerve conduction at the points where the ‘injury’ has occured.
However the main Hallmark of HNPP is the Pressure palsy, or areas of demyelination caused by fairly minimal pressure, stretch or repetitive movement. This does not follow a strict distal to proximal pattern, and could seem quite random, but usually it will in some way be a reflection of routine, lifestyle and environment. This could include other acquired or genetic physical characteristics, which may have an impact on the presentation of HNPP.
Back to demyelination. HNPP has a generalised poly-neuropathy like that of CMT1a, but unlike CMT1a it is generally of less significance than the many areas (multi) of localised (focal) entrapment-like neuropathies.
Not long after I was diagnosed I was given the opportunity to pose a question to Dr. Gareth Parry via an email group, associated with HNPP.org. Dr. Parry is a Neurologist who has taken a special interest in peripheral neuropathies, including HNPP but also Guillain-Barre Syndrome and CIDP. I wanted to know whether someone with HNPP who was totally protected from the environment and any form of ‘pressure palsy’ ( Bubble ), would develop a neuropathy over a lifetime. His answer was that there would be a strong likely hood that the person would develop a mild symmetrical distal poly-neuropathy, not unlike a mild case of CMT1a.
Demyelinating, Dysmyelinating or both
Occasionally I have seen writeups on HMSN (Hereditary Motor Sensory Neuropathies) where instead of using the term Demyelinating, Dysmyelinating has been used instead. I understand this to mean that the myelin formed is inherently dysfunctional, which can result in demyelination through early degeneration (or de for de-ath of myelin).
It seems likely that CMT1a is mainly dysmyelinating with subsequent demyelination as a result of this inherent fault of the myelin. Length dependency of the resulting neuropathy seems almost a logical conclusion. Then that would seem to suggest that HNPP has a less severe dysmyelinating length dependent neuropathy, where demyelination as a result of the inherent myelin fault (deficiency in this case) is quite mild, but the inherent fragility causes easy break down by endo and exo-environmental forces. A multifocal polyneuropathy causing recurrent episodes of entrapment-like signs and symptoms in many nerve distributions is the result.