Rae-Grant AD, Eckert NJ, Bartz S and Reed JF (1999).

Sensory symptoms of multiple sclerosis: a hidden reservoir of morbidity.

Mult Scler. 5 (3): 179-83.

Summary:
OBJECTIVE:
To assess the frequency and quality of sensory symptoms
in a population of patients with Multiple Sclerosis (MS) and compare them
with controls.

DESIGN:
Survey to target population and control group
evaluating demographic data, data on disease course, presence of various
symptoms of MS.

SETTING:
Neurological practices affiliated with a tertiary
community hospital.

PARTICIPANTS:
224 patients with MS, 93 controls of similar age and sex.

RESULTS:
Sensory symptoms were more common in MS patients than in controls, and differed in severity and quality. Fifty per cent described brief (seconds to hours) episodes of neurological dysfunction, significantly more often than in controls (P = 0.001). Pain was present at some time in similar percentages in patients and controls, but active pain problems were present more often in MS patients (P = 0.001). The qualitative description of pain in MS patients was more often neuropathic, with burning, itching, electric and formicatory pain, as opposed to throbbing, sharp or muscular pain. Pain was localized to arms, legs, trunk, hands, feet and face more often in the MS group. Lhermitte's phenomenon was present in two-thirds of patients at some time in their disease course. Twenty per cent of the patients identified themselves as having respiratory problems (Controls 7.5%, P = 0.005). Fatigue limited activity in 78% of patients, but only in 17% of controls (P = 0.001). Dizziness, memory dysfunction, and restless legs symptoms were all more frequent in patients. The self-rated 'worst' symptoms of MS was pain in 12%, fatigue in 17% and dizziness in 5%, a total of 34% of 'worst' symptoms. Sensory symptoms were present in patients with early disease and without disability as often as in disabled patients and in those with longer disease duration. There was however a strong correlation between the total number of sensory symptoms reported and the presence of disability in the MS patients.

CONCLUSIONS:
Sensory symptoms are common in MS patients. Pain syndromes, transient neurologic events, Lhermitte's phenomenon, fatigue, respiratory symptoms and vertigo were present significantly more frequently in patients with MS than in a control population and contributed to subjective morbidity. Future clinical trials assessing therapy in MS might include sensory symptoms as secondary endpoints to capture this 'hidden reservoir' of disease morbidity.

Here are some additional references  discussing the association of L'Hermitte's sign in people with MS.
 

Smith KJ and McDonald WI (1999).

The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease.

Philos Trans R Soc Lond B Biol Sci. 354 (1390): 1649-73.

Summary: The pathophysiology of multiple sclerosis is reviewed, with emphasis on the axonal conduction properties underlying the production of symptoms, and the course of the disease. The major cause of the negative symptoms during relapses (e.g. paralysis, blindness and numbness) is conduction block, caused largely by demyelination and inflammation, and possibly by defects in synaptic transmission and putative circulating blocking factors. Recovery from symptoms during remissions is due mainly to the restoration of axonal function, either by remyelination, the resolution of inflammation, or the restoration of conduction to axons which persist in the demyelinated state. Conduction in the latter axons shows a number of deficits, particularly with regard to the conduction of trains of impulses and these contribute to weakness and sensory problems. The mechanisms underlying the sensitivity of symptoms to changes in body temperature (Uhthoff's phenomenon) are discussed. The origin of 'positive' symptoms, such as tingling sensations, are described, including the generation of ectopic trains and bursts of impulses, ephaptic interactions between axons and/or neurons, the triggering of additional, spurious impulses by the transmission of normal impulses, the mechanosensitivity of axons underlying movement- induced sensations (e.g. Lhermitte's phenomenon) and pain. The clinical course of the disease is discussed, together with its relationship to the evolution of lesions as revealed by magnetic resonance imaging and spectroscopy. The earliest detectable event in the development of most new lesions is a breakdown of the blood-brain barrier in association with inflammation. Inflammation resolves after approximately one month, at which time there is an improvement in the symptoms. Demyelination occurs during the inflammatory phase of the lesion. An important mechanism determining persistent neurological deficit is axonal degeneration, although persistent conduction block arising from the failure of repair mechanisms probably also contributes.

Department of Clinical Neurosciences, Guy's, King's and St Thomas' School of Medicine, King's College, London, UK. kenneth.smith@kcl.ac.uk
 

Sakurai M and Kanazawa I (1999).

Positive symptoms in multiple sclerosis: their treatment with sodium channel blockers, lidocaine and mexiletine.

J Neurol Sci. 162 (2): 162-8.

Summary: Patients with multiple sclerosis (MS) often show positive symptoms of painful tonic seizure and dysesthesia as well as negative symptoms of paralysis and hypesthesia. Positive manifestation is paroxysmal and/or persistent. These are considered to be mediated by ectopic impulses generated at the site of demyelination, whereas negative symptoms are caused by conduction block. Conduction block at a demyelinated segment should reduce positive symptoms, but worsen negative ones. As reported previously, lidocaine, an Na channel blocker unmasks silent negative symptoms presumably by further reducing the action current in demyelinated portions and blocking conduction. Furthermore, because it blocks Na channels in a voltage- and frequency dependent manner, fibers that mediate positive symptoms are preferentially blocked. We administered lidocaine to 30 MS patients with positive symptoms. Lidocaine (mean plasma level, 2.4 pg/ml) almost completely abolished the paroxysmal manifestation of painful tonic seizures, neuralgic attacks, paroxysmal itching, and Lhermitte's sign. It also markedly alleviated persistent symptoms, but less so than paroxysmal symptoms. Similar effects were obtained with orally-administered mexiletine (300- 400 mg/day), a derivative of lidocaine, but to a lesser extent. Na channel blockers have a dual effect on symptoms in MS, depending on whether symptoms are positive or negative. The mechanism that produces positive symptoms and the effects of the drugs on these symptoms are discussed.

Department of Neurology, Graduate School of Medicine, University of Tokyo, Japan. sakuraim-neu@h.u-tokyo.ac.jp