Paroxysmal Symptoms of Multiple Sclerosis: They Come and They Go

By tscott

Denise I. Campagnolo MD, MS––Interim Multiple Sclerosis Program Director, Barrow Neurological Institute, Phoenix, Arizona

MS Attack
A multiple sclerosis (MS) attack, also called a relapse or exacerbation, is the sudden onset of new neurological symptoms or the reoccurrence of previous resolved symptoms. Further, true attacks typically last at minimum 24 hours, usually days to weeks, and generally are agreed to have to occur at least 30 days from a previous attack, so that they are separated in time.

The underlying cause of the MS relapse is inflammation in the nervous system. The inflammatory immune response strips the nerves of their insulation, or myelin, allowing the electrical signals to “short out” as they move about the nervous system. When inflammation causes the myelin to be damaged, the medical community refers to the process as demyelination. Demyelination occurs at focal points, termed “lesions” on MRI, resulting in many of the symptoms associated with MS.

Inflammation can vary in strength and location, which results in a wide-array of symptoms. Symptoms from an attack can vary from mild, such as a blurring of vision, to severe, such as complete loss of vision. They also vary in functional outcome by location: inflammation in the brain can cause problems with thinking whereas inflammation in the sensory tracts of the spinal cord may cause numbness. Typically, the formation of a new neurological symptom results from a new focal area of demyelination, or MS lesion. The deterioration of previous symptoms results from the reactivation, and subsequent worsening, of an old MS lesion. (http://www.nationalmssociety.org/about-multiple-clerosis/treatments/exacerbations/index.aspx).

Pseudoexacerbation
Many people with MS often confuse a pseudoexacerbation with a true MS exacerbation. The symptoms are similar, but the duration and underlying cause are not. A true exacerbation corresponds to advancing inflammation from the MS disease, as we discussed above. A pseudoexacerbation, on the other hand, is the temporary aggravation of existing symptoms.

In almost every case, a pseudoexacerbation results from an increase in body temperature. This increase may come externally, such as from the sun or otherwise high temperatures, or internally, such as from a fever or hormonal changes. Heat presents a problem since the nervous system does not operate correctly at higher temperatures. The messages that had previously flowed seamlessly between the brain, spinal cord, and peripheral nerves now contain “static” induced by the heat. This “static” is easily compared to static on a radio: the messages are getting where they need to go, but they are unclear and parts of our bodies are unable to understand. As long as the patient’s body heat remains elevated, the symptoms will not go away. When a patient with MS starts to feel the effects of a pseudoexacerbation, the best treatment is to cool down the body. Symptoms will often subside on their own, leaving no new or different long-term effects. (O’Connell, 2004)

Paroxysmal Symptoms
Now let’s get to the topic of this article, the paroxysmal symptoms of MS. Further distinction is necessary for these symptoms, as compared to exacerbations and pseudoexacerbations. Paroxysmal symptoms are defined as temporary neurological disturbances, such as muscle spasms (called tonic spasms), numbness and tingling sensations (called paresthesias), slurred speech, imbalance (called ataxia), and so forth. They may mimic symptoms of MS attacks, but the difference is that they are fleeting, from several seconds up to 2 minutes, rather than persistent over several days to weeks as described in MS attacks. Paroxysms, as these symptoms are also referred to, are not the result of heat, as described in cases of pseudoexacerbation.

In addition to their shortness in length, paroxysmal symptoms occur over and over again from a few times a day to a few times an hour. They can be triggered by exercise, hot baths, smoking, emotions, neck flexion, and eye movements, although they often appear out of nowhere. These symptoms may last from a few days up to several months, but will eventually go away (Twomey and Espir, 1980). Like the MS attack, paroxysmal symptoms vary greatly from person to person. I will discuss the common paroxysmal symptoms in greater detail below.

Muscle Spasms (Tonic Spasms)
Spasticity is one of the most common symptoms of MS. Muscle spasms can belong to one of two categories. First, spastic hypertonia results from an upper motor neuron injury and is not unique to MS. The condition is usually permanent after injury and is characterized by stiffened muscles (tone) and sudden, jerking muscle movements. Spastic hypertonia does not come and go, but rather, refers to the “everyday” spasticity associated with neurological dysfunction. This is not a paroxysmal symptom, but rather, a core symptom of MS, and is treated by medications such as baclofen and tizanidine.

Researchers refer to the second type of spasm as “paroxysmal dystonia” or tonic spasms. Tonic spasms are short, but frequent, muscle spasms that often result in pain. MS researchers further classify paroxysmal spasms as stereotyped, meaning they occur over and over again with little variation until they eventually go away. Hyperventilation seems to be a key trigger in initiating this type of spasm (Honig, Wasserstein, & Adornato, 1991). When tonic spasms occur in the torso muscles, we call them “MS hugs” since it feels like a person is gripping the patient around the torso for the length of the spasm.

Numbness and Tingling
Paroxysmal sensory disturbances, such as numbness or tingling (paresthesias), are a very common occurrence in MS. They range from minimal deficits, such as tingling in the extremities, to severe, such as complete numbness that disrupts functional tasks. These symptoms can often accompany tonic spasms. Paroxysmal itching can also occur.

Motor Speech Disorders (Dysarthria)
Motor speech dysfunction is another common paroxysmal symptom associated with MS. The medical community refers to this phenomenon as paroxysmal dysarthria. It often results from unusual activity or electrical impulse disruption within the speech-controlling portions of the brain. Among a wide variety of symptoms, common speech problems include long pauses between words and slurred or nasal sounding speech. Usual treatment involves therapy with a qualified speech pathologist.

Balance Problems (Ataxia)
Often accompanying speech disorders are problems with walking and balance, referred to as paroxysmal ataxia. Ataxia may appear as a “drunken” stumble resulting from balance issues. Sensory ataxia can result from severe numbness in the feet and legs. Imbalance occurs since the patient with MS may not know where their feet are in the course of walking. Severe ataxia often requires use of an assistive device such as a walker.

What Causes Paroxysmal Symptoms?
Exploring methods to prevent paroxysmal symptoms required researchers to investigate the biological causes behind them. As we mentioned in reference to the MS relapse, the autoimmune response in MS causes inflammation and subsequent removal of the myelin insulation found on nervous tissue. Axons carry signals up and down the spinal cord, and they are often called the electrical wiring of the nervous system. The signals that the nervous system uses to communicate are carried in the form of electric impulses, called an action potential by the medical community. Removal of the myelin insulation causes these impulses to “short out,” preventing proper communication between cells. Researchers call this conduction blocking because axons can no longer carry the electrical impulses necessary to communicate movement or sensory information. Conduction blocking can lead to severe functional losses such as blindness or paralysis (Smith & McDonald, 1999).

Ectopic Transmission
Research suggests that in addition to blocking signal transmission, demyelinated axons can also become overexcitable at the MS lesion. Consequently, axons may begin to fire electrical impulses that do not originate at the appropriate sites within the brain and sensory neurons. Rather, the nerve impulse begins inappropriately at the site of demyelination, sending a signal out in both directions. This occurs due to the flow of ions, such as potassium and sodium, from the outside of the neuron into the long, branching part of the neuron called the axon. These ions carry positive charges and can trigger the axon to fire at the site of demyelination. Consequently, axon firing occurs spontaneously and independently. Such inappropriate firings, termed ectopic transmission, result in some of the paroxysmal symptoms that we have talked about (Smith, Felts, & Kapoor, 1997).

Ephaptic Transmission
Ephaptic transmission adds to the reasons why paroxysms occur. We know that ectopic transmission occurs on its own, suggesting that many demyelinated axons sit poised on the fence, ready and waiting to produce a nerve impulse. Therefore, at the MS lesion, just a little change in charge will cause the axon to fire. Researchers believe that the current generated by active axons passing nearby the demyelinated region is enough to trigger the nerve impulse (Smith & McDonald, 1999). Arvanitaki demonstrated that when two invertebrate axons are laid side-by-side, a nerve impulse in one can sometimes cause a nerve impulse in the other. He conducted the experiment with fully myelinated axons outside of a living environment (Arvanitaki, 1942). The over-excitability of demyelinated axons in MS may increase the likelihood of this process. In fact, Rasminsky demonstrated ephaptic transmission in a live, experimental mouse between a normal and an axon with myelin damage (Rasminsky, 1980).

Researchers have designated the phrase “ephaptic transmission” to refer to the process in which one axon causes a neighboring axon to fire. Rather than uncoordinated, spontaneous firings resulting from ectopic transmission, ephaptic transmission results in the collective, simultaneous firing of a number of axons (Smith, Felts, & Kapoor, 1997). The synchronized firing of a group of damaged axons more accurately describes some paroxysmal symptoms since single axon firing is barely noticed by the patient. Some paroxysmal symptoms in patients with MS seem to provide evidence for ephaptic transmission at work. For example, touching a patient lightly on the shoulder may cause both the touch sensation as well as pain in the same area. It seems that the normal touch nerve impulse travels through a site of demyelination, recruiting demyelinated pain axons to inappropriately fire as well (Smith & McDonald, 1999).

Treatment of Paroxysmal Symptoms
When paroxysmal symptoms are minor, medication is often unnecessary. These symptoms come and go on their own. Reassuring the patient that the symptoms will likely go away soon can calm their apprehension. Adaptive devices can also supplement function when these symptoms flare up. For instance, in cases of balance problems (called intermittent ataxia), the patient may use a walker as a precaution to prevent falls.

In situations where paroxysmal symptoms interfere with daily-living, medications can offer some relief. Anti-epilepsy drugs (Table 1) are currently used to reduce paroxysmal symptoms, but ongoing research continues its search for more effective treatments. We will discuss several anti-epilepsy drugs proven to be effective or show promise to treat paroxysmal symptoms.

Carbamazepine (Tegretol)
Carbamazepine has long been used in treatment of paroxysmal pain and tonic spasms and the effectiveness is well-established. The drug is believed to block sodium channels and the flow of charged sodium ions, and consequently causes a reduction in the random firing of axons stripped of their myelin (Honig, Wasserstein, & Adornato, 1991). High occurrences of bad side effects, however, have been reported with carbamazepine. One study reported bad effects in 20 out of 36 patients treated with the drug. Most concerning was that 12 of these patients experienced a worsening of neurological function, in effect, appearing as an MS relapse. These researchers believe that blocking sodium channels may be effective in preventing paroxysmal symptoms, but it may simultaneously induce a worsening of the core MS symptoms (Solaro et al., 2005).

Oxcarbazepine (Trileptal)
Oxcarbazepine is a close relative of carbamazepine. It acts in much the same way, blocking sodium channels to prevent unintended discharges of nerve impulses. Consequently, it may also cause a worsening of core MS symptoms, although this risk has not been explored. It has only recently been approved to treat seizures. A recent study suggests that oxcarbazepine may be effective in the treatment of paroxysmal pain. The study included 12 patients with MS with paroxysmal pain who were either intolerant or unresponsive to previously approved anti-epileptic medications. Nine of the 12 patients experienced complete recovery from paroxysmal pain symptoms after one month of treatment with oxcarbazepine. Two patients dropped out due to bad side effects, neither related to worsening neurological status. This study was effective in demonstrating promise, but a larger, randomized, double-blind study is required to establish tolerance and effectiveness of the drug (Solaro, Restivo, Mancardi, & Tanganelli, 2007).

Gabapentin (Neurontin)
Gabapentin is another anti-epileptic drug found to be effective in preventing paroxysmal symptoms. The exact way it works is unknown. Experimental evidence, however, suggests that gabapentin increases gamma aminobutyric acid (GABA) levels in the brain. GABA is a chemical that helps decrease electrical impulse activity. In an informal trial, 21 patients suffering from a wide-variety of paroxysmal symptoms were evaluated with treatment of gabapentin. Eighteen of the 21 patients showed improvement or complete recovery over the course of a 3-month period, suggesting effectiveness in treating paroxysmal symptoms. Although a proper double-blind, randomized study is lacking in patients with MS, gabapentin is regarded as a standard medication to treat paroxysmal symptoms (Solaro et al.,1998).

Conclusions
Paroxysmal symptoms of MS can appear suddenly, go away equally suddenly and may occur many times in a day or even an hour. Paroxysmal symptoms have even been described in some cases as the presenting symptoms of MS. They are highly characteristic of MS and will typically respond to medication. So I encourage you to discuss any bothersome paroxysmal symptoms you have with your MS professional, and feel reassured that you are not “going crazy”. These symptoms are real, they have a biological origin, and will typically respond to medical management.

References
Arvanitaki, A. (1942). Effects evoked in an axon by the activity of a contiguous one. Journal of Neurophysiology, 5, 89-108.

Honig, L. S., Wasserstein, P. H., & Adornato, B. T. (1991). Tonic spasms in multiple sclerosis: Anatomical basis and treatment. The Western Journal of Medicine, 154(6):723-726.

National Multiple Sclerosis Society (2008). Retrieved 09.09.2008 from: http://www.nationalmssociety.org/about-multiple-clerosis/treatments/exacerbations/index.aspx

O’Connell, D. (2004). Is it in MS attack––or not? Inside MS, July-September, 58-63.

Rasminsky, M.(1980). Ephaptic transmission between single nerve fibers in the spinal nerve roots of dystrophic mice. Journal of Physiology, 305, 151-169

Smith, K. J., & McDonald, W. I.(1999). The pathophysiology of multiple sclerosis: The mechanisms underlying the production of symptoms and the natural history of the disease. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 354, 1649-1673.

Smith, K. J., Felts, P.A., & Kapoor, R. (1997). Axonal hyperexcitability: Mechanism and role in symptom production in demyelinating diseases. Neuroscientist, 3, 237-246.

Solaro, C., Brichetto, G., Battaglia, M. A., Messmer Uccelli M., & Mancardi, G. L. (2005). Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study. Journal of the Neurological Sciences, 25, 307-310.

Solaro, C., Restivo, D., Mancardi, G. L., & Tanganelli, P. (2007). Oxcarbazepine for treating paroxysmal painful symptoms in multiple sclerosis: A pilot study. Journal of the Neurological Sciences, 28, 156-158.

Solaro, C., Lunardi, G. L., Capello, E., Inglese, M., Messmer, Uccelli M., U., et al. (1998). An open-label trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients. Neurology, 51, 609-611.

Twomey, J. A., & Espir, M. L. (1980). Paroxysmal symptoms as the first manifestations of multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, 43, 296-304.

2 Responses to “Paroxysmal Symptoms of Multiple Sclerosis: They Come and They Go”

  1. PJ Madore

    As a person diagnosed with M.S. since 1995 and just recently experiencing an extended period (weeks) of tingling/burning sensations at varying body locations I found your article while searching the web for information.

    After reading the information from your Paroxysmal Symptoms section:
    snip-
    “These symptoms may last from a few days up to several months, but will eventually go away.”

    I’m wondering why anyone would want to chance the numerous side effects of any of the meds you list at the end of the article.

    Perhaps I’m fortunate to be at home and more able to wait out the daily sensations if I can believe they will eventually go away. I might be more willing to risk taking the meds if I had to be more job-productive each day.

    At any rate, thank you for the information. After experiencing ongoing muscle spasms and some stiffened muscle tone for many years it’s been surprising to me to have these several-per-day burning sensations.

    PJMadore
    Delaware, USA

    #6905
38336
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