Temperature And Conduction Block In Multiple Sclerosis

In Nerve Conduction studies, it may be difficult to distinguish Conduction Block from increased temporal dispersion.

We assessed whether a better distinction is possible by warming, because this increases the number of blocked Nerve Fibers and decreases temporal dispersion.

We investigated 11 patients with Conduction Block in the Median or Ulnar Nerve. Motor conduction was studied at 25 degrees C and at 40 degrees C.

The amplitude reduction and area reduction were significantly greater at 40 degrees C than at 25 degrees C.

Significantly more nerve segments fulfilled criteria for Conduction Block at 40 degrees C than at 25 degrees C.

The duration prolongation was slightly smaller at 40 degrees C.

These results indicate that, in DeMyelinating NeuroPathies, an increase in temperature increases the number of blocked Nerve Fibers and decreases temporal dispersion.

Conduction Block may therefore be missed when the investigated limb is too cold.

Based on our study, we also propose a criterion for Conduction Block that is based on the influence of temperature.

Temperature thresholds were determined in 16 patients with Probable or Definite Multiple Sclerosis, in six patients with Possible but unconfirmed Multiple Sclerosis and in 34 healthy subjects, using the method of limits and the Thermal Sensory Limen (TSL) of the MarStock technique.

A significant proportion of the patients had Thresholds outside the 2.5 SD range for normal subjects, both for warmth detection Threshold and TSL.

In addition, 10 patients with Probable or Definite Multiple Sclerosis and one patient with Possible Multiple Sclerosis reported a paradoxical heat sensation, i.e. a sensation of warmth elicited by a cold stimulus.

This illusion was almost exclusively observed with the alternating warm and cold stimuli of the TSL procedure. In contrast to experimental Nerve Block or Peripheral DeMyelinating Neuropathy.

Where paradoxical heat sensation has been described by various authors, in the patients with Multiple Sclerosis the DeMyelination sites were located in the Central Nervous System.

The observation that Multiple Sclerosis patients had paradoxical heat sensation in addition to Threshold abnormalities supports the view that SupraSpinal sites are important for the integration of temperature sensation.

In 1890, Uhthoff studied Multiple Sclerosis (MS) patients who developed Amblyopia following exercise (Uhthoff's Syndrome), a phenomenon later discovered to be secondary to elevated body temperature from muscular activity.

Six decades later, the hot bath test and various other Heating Reactions (HR) began to be used diagnostically. They were essentially discontinued after 1983, being replaced by more specific and safer tests and procedures.

Over 80% of MS patients develop a panoply of Neurological signs during HyperThermia, 60% of which are "new" to that patient.

The literature contains a number of unexplained paradoxical responses of MS patients during induced HyperThermia.

These challenge the current hypothesis that, in MS, HyperThermia induces a heat-linked Neuro-blockade of partially DeMyelinated Axons.

Some MS patients developed signs before temperature elevations occurred; others showed clearing of signs while temperatures were elevated or were ascending.

Several MS patients improved for about 3 hours after being tested, a rebound phenomenon known as "overshoot." Conversely, other MS patients developed persistent Neurological deficits after HyperThermia.

The etiology of HR may be multifactorial. This includes heat itself, effects of Serum Calcium, blockade of Ion channels, circulatory changes, Heat Shock Proteins, and unidentified Humoral substances.

Research techniques are suggested to continue investigations into the enigma of HR, hopefully to widen knowledge of DeMyelination.

This is a study of 13 Malaysian patients with Clinically Definite Multiple Sclerosis (MS) subjected to a hot bath test with VEPs, BAEPs, Median Nerve SSEPs before and after heating.

Five patients (38%) developed Neurological changes with the rise in body temperature. There was an average of 0.46 new sign per patient.

Four patients had motor disturbances attributed mainly to aggravation of Spinal Cord dysfunction.

Two patients had additional Visual deterioration, one patient has associated VEP change.

This study shows that though Uhthoff's Phenomenon has not been noted in the reports of Asian MS patients, when subjected to rigorous testing, Asian MS patients also show sensitivity to body temperature change.

However, the percentage of positivity of the hot bath test is much lower than that reported for Caucasians. Thus this study shows further differences between Asian and Caucasian MS patients.

Clinical manifestations of Multiple Sclerosis cannot always be correlated with the type of lesion present.

Plaques in certain regions may be clinically silent whereas, inversely, some Neurological disorders appear not to be related to a DeMyelination process.

The PathoPhysiology of Neurological symptoms and signs in Multiple Sclerosis may therefore be related to two other factors:

1. Membrane phenomena observed in DeMyelinated fibers and leading to partial or complete Conduction Block
2. Conduction Blocks due to pathological phenomena that fail to provoke anatomical DeMyelination

DeMyelination induces a sudden drop in Impedance of the Axon membrane which is responsible for the Conduction Block.

Redistribution of Sodium IonoPhores in the DeMyelinated Axon enables transmission of certain messages, but in a slower and unreliable manner.

Sensitivity of DeMyelinated fibers to temperature and the ExtraCellular Ionic environment provides an explanation for the transient, recurrent stereotyped reactions provoked by fever, physical exercise or digestion.

In the absence of DeMyelination, a Conduction Block could be the result of either a minimal lesion at the ParaNodal Myelin with denudation of the specialized parts between Axon and Glia, or of Humoral blocking factors - of debatable specificity - or Cellular factors that have been demonstrated recently.

The existence of such mechanisms suggests the need for revision of the notion of acute episodes of Multiple Sclerosis.

Finally, knowledge of the mechanisms involved in Nerve Conduction along DeMyelinated fibers suggests the possibility of therapy to restore Conduction of these fibers by acting on ExtraCellular Ionic concentrations or directly on membrane Ionic canals.

Aggravation of Neurological symptoms in MS patients in heating is well known. This phenomenon is explained by the change of Conduction in DeMyelinated Nerve fibers.

In raised temperature Conduction Block occurs. The Threshold of Conduction Block dependent on temperature, is probably proportional to the degree of DeMyelination.

It is possible to inhibit this effect by Tyrosin. This model may present a view to a part of NeuroPhysiological mechanisms of MS, on which we possibly can take therapeutical influence.

By way of a questionnaire 125 MS patients were asked about changes of their symptoms in heating or cooling. 93% had marked sensitivity to heating.

In 90% worsening of Neurological symptoms or of general feeling occured in a hot bath. On the other hand about half the patients reported improvement in a cold bath.

Therefore we suggest, that a noticeable part of Neurological deficit is reversible, if we were able to raise the Threshold of Conduction Block, which depends on temperature, ph, Electrolytes and NeuroTransmitters.

The effects of raising body temperature on the Visual (VEP) and SomatoSensory Evoked Potentials (SSEP) were observed in normal subjects and in patients with Multiple Sclerosis.

The amplitude of the VEP was significantly reduced to the same degree after heating in normal subjects and in patients with Multiple Sclerosis but there was no effect on the latency of the potential.

Changes in amplitude could not be related to reduction in Visual Acuity.

In contrast, the Cervical SEP was greatly disorganized after heating in many patients with Multiple Sclerosis while the only effect in normal subjects was to reduce the latency, by increasing Peripheral Conduction Velocity.

These results suggest that heat caused Conduction Block in DeMyelinated Axons in the Sensory Pathways of the Cervical Spinal Cord.