Heterozygosity for neuronal ceroid lipofuscinosis predisposes to bipolar disorder

Objective: Bipolar disorder is a heritable chronic mental disorder that causes psychosocial impairment through depressive/manic episodes. Familial transmission of bipolar disorder does not follow simple Mendelian patterns of inheritance. The aim of this study was to describe a large family with 12 members affected by bipolar disorder. Whole-exome sequencing was performed for eight members, three of whom were diagnosed with bipolar disorder, and another reported as "borderline." Methods: Whole-exome sequencing data allowed us to select variants that the affected members had in common, including and excluding the "borderline" individual with moderate anxiety and obsessive-compulsive traits. Results: The results favored designating certain genes as predispositional to bipolar disorder: a heterozygous missense variant in CLN6 resulted in a "borderline" phenotype that, if combined with a heterozygous missense variant in ZNF92, is responsible for the more severe bipolar disorder phenotype. Both rare missense changes are predicted to disrupt protein function. Conclusions: Loss of both alleles in CLN6 causes neuronal ceroid lipofuscinosis, a severe progressive childhood neurological disorder. Our results indicate that heterozygous CLN6 carriers, previously reported as healthy, may be susceptible to bipolar disorder later in life if associated with additional variants in ZNF92.

Peripheral electrical nerve stimulation in chronic post-surgical pain: Let's try!

Chronic post-surgical pain [CPSP] is a common complication after surgery, which has significant effects on quality of life with restriction of activities of daily living, and it is associated with increased analgesic use. The incidence of CPSP has wide variations among different surgical procedures and this can be due to difference in definition of CPSP and small sample size studies. The mechanisms of CPSP are complex, poorly understood, and many patients show neuropathic pain features. CPSP is often refractory to medical and interventional management and it may have profound consequences for the quality of life of the patient. Percutaneous electrical nerve stimulation [PENS] can be an effective treatment for management of neuropathic pain and may be a viable treatment option that should be considered when other treatments fail. The aim of these case reports is to encourage the use of PENS in the management of CPSP and to motivate further studies on the use of PENS in this field. We present a case report of two patients with CPSP and features of neuropathic pain, refractory to other pharmacological treatments and successfully treated with one-day trial of PENS. The aim of this article is to underline the possible role of Peripheral Electrical Nerve Stimulation [PENS] in the management of Chronic Post-Surgical Pain and to encourage further studies on the use of PENS in this field