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Mexiletine is effective on segmental hyperhidrosis: report of two cases
  1. S Ishibashi1,
  2. T Yokota1,
  3. A Inaba1,
  4. M Yamada1,
  5. H Mizusawa1,
  6. T Iwai2,
  7. T Shiojiri3
  1. 1Department of Neurology, Tokyo Medical and Dental University School of Medicine, 1–5–45, Yushima, Bunkyo-ku, Tokyo 113–8519, Japan
  2. 2Department of Surgery, Division of Vascular Surgery
  3. 3Department of Neurology, Asahi General Hospital, I- 1326, Asahi, Chiba, 289-2511, Japan
  1. Correspondence to:
 Dr T Yokota;
 tak-yokota.neuro{at}tmd.ac.jp

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Segmental hyperhidrosis occurs in patients who have spinal cord lesions such as syringomyelia,1 vascular disorders, or tumours. Severe segmental hyperhidrosis not only causes discomfort, but may disturb daily life, as it did with our patients. There have been no reports on the treatment of segmental hyperhidrosis. We report on two patients with segmental hyperhidrosis caused by syringomyelia and cavernous haemangioma of the spinal cord, in which oral administration of mexiletine ameliorated the symptoms.

A 41 year old woman experienced dysaesthesia of the left side of the trunk, which gradually progressed. At the age of 56 she developed dysaesthesia of the left upper limb as well. At that time, she had excessive sweating on the left side of her face, trunk, and upper limb, even when it was not hot, and had to change her nightwear a few times each night. Neurological examination detected dissociated sensory disturbance in the left half of the trunk in the Th2-Th4 area. Hyperhidrosis was present on the left side from the face to the trunk at the Th7 level. Deep tendon reflexes were normal with no pathological reflexes. This hyperhidrosis distribution was confirmed by the Minor test and quantified with a Servomed evaporimeter. Thermography showed reduced body temperature of the same distribution as hyperhidrosis. Radiography detected scoliosis at Th1-Th9. Magnetic resonance imaging showed syringomyelia prominent at Th2-Th4. No Chiari malformation was present. Her hyperhidrosis was relieved by the oral administration of 200 mg/day mexiletine (fig 1). Oral administration of 400 mg/day carbamazepine also gave partial relief. She did not have to change her nightwear and could sleep well.

A 56 year old man at first experienced increased sweating on both sides of the upper limbs and trunk, and from the age of 58 hyperhidrosis on his face. He had to change his clothes several times a day. His clinical symptoms slowly progressed, and at the age of 63, he was admitted to our hospital. Neurological examination showed bilateral hypaesthesia at Th2-Th5 and hyperhidrosis from the face to the dermatome Th10 level on both sides. Deep tendon reflexes were normal with no pathological reflexes. Hyperhidrosis was confirmed by the Minor test and quantified with a Servomed evaporimeter. Thermography showed decreased body temperature over the same area as the hyperhidrosis was distributed. Magnetic resonance imaging showed a cavernous haemangioma at Th2-Th5. His hyperhidrosis was relieved by oral administration of 200 mg/day mexiletine (fig 1). Oral administration of 400 mg/day carbamazepine also gave partial relief. He did not have to change his clothes during the day.

In addition, we tried mexiletine to eight patients (five women, age range 18–34 years) with primary hyperhidrosis, which is defined as excessive, uncontrollable sweating without any discernible cause. No improvement was noted after oral administration of 200 mg/day mexiletine.

This is the first report of the use of mexiletine to treat segmental hyperhidrosis. Three mechanisms have been hypothesised as possible causes of segmental hyperhidrosis brought about by spinal cord lesions: (1) disinhibition of preganglionic sympathetic neurons due to interruption of the inhibitory descending pathway,2 (2) overactivity of preganglionic sympathetic neurons due to spinal cord lesions,3 and (3) autonomic hyperreflexia due to cutaneous stimulation, such as postural change, or bladder and intestine stimulation.4

We judge that the mechanism of segmental hyperhidrosis in our patients was produced by overactivity of the preganglionic sympathetic neurons. The intermediolateral nucleus, located in the lateral horn of the spinal cord from C8-Th1 to L2-L4, receives both excitatory and inhibitory descending innervations from the thalamus. The face and neck are innervated by the intermediolateral nucleus at the Th2-Th4 level, in the upper limbs at Th2-Th8, in the trunk at Th6-Th10, and in the lower limbs at Th11-Th12. The ambiguous, overlapping innervation by the intermediolateral nucleus accounts for the differences in the distributions of the sensory disturbances and hyperhidrosis caused by the same spinal cord lesion. In fact, the hyperhidrosis distributions in our patients corresponded to the area innervated by the intermediolateral nucleus at the levels of the lesions seen on MRI and of the sensory deficits. This hyperhidrosis distribution cannot be explained by interruption of the inhibitory descending pathway. Because hyperhidrosis in our patients occurred even without cutaneous stimulation, we suspect persistent spontaneous overactivity of the preganglionic sympathetic neurons due to spinal cord lesions.

Oral administration of mexiletine was an excellent remedy for the segmental hyperhidrosis of our patients. Mexiletine is a sodium channel blocker reported to be effective for treating painful neuropathies.5 In terms of its mechanism, mexiletine is thought to inhibit the spontaneous activity of regenerating fibres in the spinal cord or to act on the spinal mediated nociceptive flexor reflex.5 We consider it compatible that in our patients mexiletine inhibited the spontaneous activity of the intermediolateral nucleus caused by spinal cord leisons. Our findings indicate that sodium channel blockers, such as mexiletine and carbamazepine, should be considered for the treatment of segmental hyperhidrosis caused by spinal cord lesions.

Figure 1

The sweat rate (mg/cm2/min) was determined with a Kens-Perspiro OSS-100 (Suzuken Co Ltd.). All measurements were made at the Th4 level in the spine. The room was maintained at 60±1% humidity and 36±1°C. Sweat rates were measured for both patients and five healthy men (mean age 53.6 years) and five women (mean age 42.3 years). Data for the patients were obtained before treatment (open circles ) and after oral administration of 200 mg/day mexiletine (closed circles).

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