Israel Medical Association Journal

Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment.

Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel.

Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined.

Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain.

Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.

Background: Spasticity is a common neurologic disorder with adverse effects on the patient's function. Conservative management is unsuccessful in a significant proportion of patients and neurosurgical intervention should be considered. The mainstay of surgical treatment of spasticity is selective posterior rhizotomy, i.e., section of sensory nerve roots of the cauda equina.

Objective: To report our experience with selective posterior rhizotomy in the treatment of spasticity.

Methods: We retrospectively reviewed our experience in 154 patients who underwent SPR during 30 years. The indication for surgery was spasticity that significantly hindered the patient's function or care and was resistant to conservative treatment. All patients were evaluated for spasticity in the lower and upper limbs, the presence or absence of painful spasms, and sphincter disturbances. The decision

as to which roots to be sectioned, and to what extent, was based mainly on clinical muscle testing.

Results: Reduction of spasticity in the lower limbs was obtained in every case, with improvement in movements in 86% of cases. Painful spasms were alleviated in 80% of cases. Amelioration of neurogenic bladder was observed in 42%. A minority of the patients also showed improvement in speech and cognitive performance. There was no perioperative mortality or major complications.

Conclusion: SPR is a safe and effective method for the treatment of spasticity with long-lasting beneficial effects. We suggest that this method be considered more frequently for patients with spasticity that interferes with their quality of life.