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Recurrent Uhthoff's: Is there a progressive element?

Posted: Tue Jun 11, 2013 12:35 pm
by sardi
I was diagnosed w/ ms last June after I developed optic neuritis. While vision in my left eye is only slightly off at this point, it does get worse after a too hot shower or not being careful during exercise. It always returns to its baseline (I think) but I'm wondering if this repetitive heat-induced dropping or slowing of axonal activity is causing any lasting damage to my optic nerve (or any nerve!). Has anyone come across any reading on this or personally experienced a permanent decrease in function after a 'uhthoff event' that was not due to a flare-up?
thanks

Re: Recurrent Uhthoff's: Is there a progressive element?

Posted: Tue Jun 11, 2013 6:16 pm
by Annesse
Hi sardi~An increase in nitric oxide may be partly to blame for your vision decline upon heat exposure.

Here is one study that discusses the connection to nitric oxide and optic neuritis. Notice the extremely high levels found in MS patients.

Nitric oxide in Optic Neuritis and Multiple Sclerosis
Chuman, Hideki MD, PhD


There has been an explosive growth of research on the role of nitric oxide (NO) in physiological and pathologic processes in the brain. Physiologically, NO functions as a neurotransmitter and a vasodilator for fine local control of cerebral blood flow. In pathologic states, NO is induced in response to various inflammatory conditions.

In this issue of the Journal of Neuro-Ophthalmology, Tsoi et al (1) report evidence for inducible nitric oxide synthase (iNOS) and peroxynitrite-mediated damage in optic neuritis (ON). The article is worth noticing because the optic nerves were obtained from a single patient with clinically isolated ON who died of causes unrelated to ON. Significantly, the patient was in clinical remission and undergoing interferon therapy. The authors compared the immunohistochemical findings in the patient with ON to control normal optic nerves obtained from an eye bank. In the patient with ON, the authors showed localized loss of myelin proteins, myelin breakdown, and the presence of iNOS and nitrotyrosine associated with inflammatory infiltrates on the edges of the nerve and reactive astrocytes. This evidence implicates the role of iNOS in the inflammation and demyelination of ON. Similarly, increased iNOS activity has been demonstrated in astrocytes in demyelinating lesions of postmortem tissues in multiple sclerosis (MS) (2). In addition, a 70% elevation in cerebrospinal nitrite has been reported in living patients with MS (3).


[So, anything that causes a further increase in nitric oxide could potentially cause damage to the optic nerve.]

Nitric oxide is involved in temperature regulation. In the following study the researchers stated that during whole-body heat stress a great increase in skin blood flow is necessary to dissipate body heat and that several studies have demonstrated that nitric oxide participates significantly in this increase.

J Physiol. 2008 February 1; 586(Pt 3): 689–690.
In vivo vasodilating mechanisms: who's NOS involved?
D Sigaudo-Roussel, B Fromy, and J L Saumet

“The human skin circulation has a key role in thermoregulation via responses to both reflex whole-body and local thermal stimuli…During whole-body heat stress, a great increase in skin blood flow is necessary to dissipate body heat… several studies have demonstrated that nitric oxide (NO) participated significantly in skin blood flow increase induced by whole-body heat stress…”


An overproduction of nitric oxide could contribute to the heat intolerance common to many MS patients. In the following study published in Neurology researchers from the Netherlands and Russia monitored 10 people with multiple sclerosis that had heat induced fatigue. The patients were cooled with special clothing and a sharp decrease in levels of fatigue was reported. The researchers noted that inner body temperatures did not drop during the experiment, which was to be expected, considering the body’s mechanisms for keeping core temperatures stable.
Instead, they pointed to nitric oxide levels, which dropped in the patients who had been cooled.


Neurology. 2001 Sep 11;57(5):892-4.
Cooling garment treatment in MS: clinical improvement and decrease in leukocyte NO production.
Beenakker EA, Oparina TI, Hartgring A, Teelken A, Arutjunyan AV, De Keyser J.

“Ten heat-sensitive patients with MS were randomly allocated in a cross-over study to wear a cooling garment for 60 minutes at 7 degrees C (active cooling) and 26 degrees C (sham cooling). In contrast to sham cooling, active cooling improved fatigue and postural stability with eyes closed and muscle strength. There was no decrease in tympanic temperature, but active cooling was associated with a 41% decrease in mean leukocyte nitric oxide (NO) production…”

Re: Recurrent Uhthoff's: Is there a progressive element?

Posted: Wed Jun 19, 2013 6:28 am
by erimus
My uthoffs is similar - it takes a very small increase in temperature to affect my vision. It also causes weakness in my legs. The nitric oxide link sounds interesting. Does anyone know of practical ways to reduce NO?

Re: Recurrent Uhthoff's: Is there a progressive element?

Posted: Wed Jun 19, 2013 11:53 am
by mrbarlow
erimus wrote:My uthoffs is similar - it takes a very small increase in temperature to affect my vision. It also causes weakness in my legs. The nitric oxide link sounds interesting. Does anyone know of practical ways to reduce NO?
Uric Acid scavenges peroxinitrite so Inosine maybe helpful as it raised serum uric acid.

Re: Recurrent Uhthoff's: Is there a progressive element?

Posted: Wed Jun 19, 2013 4:50 pm
by eric593
I have suffered from uhthoff's for probably more than a decade. Yet every time my optic nerves are examined, they continue to have a normal, healthy appearance.

So it does not appear that continuing uhthoff's has had any detrimental, deteriorating effect on my optic nerves.