Paradoxical worsening of seizure activity with pregabalin in an adult with isodicentric 15 (IDIC-15) syndrome involving duplications of the GABRB3, GABRA5 and GABRG3 genes.

BACKGROUND: Isodicentric 15 syndrome (IDIC-15) is due to partial duplications of chromosome 15 that may includes the q11-13 region that includes genes encoding the α5 (GABRA5) and ß3 - γ3 (GABRB3) receptor subunits. The disease causes intellectual and physical developmental delay, seizures, intellectual disability and behavioral disorders that may be related to abnormal GABA receptor function and morphology. Seizures are often severe and may be refractory to treatment. There are however no specific guidelines for the treatment of the seizures and it is unknown whether drugs that affect the GABAergic system have a different effect in IDIC-15 seizures. CASE PRESENTATION: We report the case of an adult individual with IDIC-15 whose complex-partial seizures worsened dramatically after the introduction of pregabalin, with increased seizure frequency, frequent generalization, and appearance of new seizure pattern. Her cognitive function and verbal skills also worsened during treatment with pregabalin. Her seizures and cognitive skills quickly improved after pregabalin was discontinued and treatment with lacosamide started. DISCUSSION: As her genetic testing confirmed that her region of duplication included GABA receptor encoding genes, it is plausible that the worsening of seizures were due to induction of an abnormal GABAergic response to pregabalin. CONCLUSION: As her genetic testing confirmed that her region of duplication included GABA receptor encoding genes, it is plausible that the worsening of seizures were due to induction of an abnormal GABAergic response to pregabalin.This case may help define proper therapeutic strategies for the treatment of IDIC-15 associated seizures.

Triple (interferon, ribavirin, amantadine) versus double (interferon, ribavirin) re-therapy for interferon relapser genotype 1b HCV chronic active hepatitis patients.

BACKGROUND: Retreatment for 6 months with the association ribavirin-interferon of HCV-related chronic active hepatitis relapser patients has high probability of failure, mostly in those with genotype 1b. We evaluated the efficacy of extending the therapy from 6 to 12 months without or with the addition of amantadine. METHODS: Forty-nine genotype 1b relapser patients were treated with 3 MU of IFN-alpha2b three times per week and ribavirin 1000-1200 mg daily (double therapy). Twenty-four patients, who did not respond after 6 months of treatment, were randomized to continue for further 6 months either with the same schedule or with also the addition of amantadine 200 mg daily (triple therapy). RESULTS: A sustained virological response was observed in 15/37 subjects (41%) treated for 12 months of double therapy. In the arm of the study evaluating amantadine, end of treatment virologic response was observed in 0/12 patients of double therapy group and in 4/12 of triple therapy (P=0.09). After 6 months of follow-up, a sustained virologic response (SVR) was observed in two patients treated with the triple therapy. CONCLUSIONS: This study confirms poor results of retreatment (even if 12 months double or triple therapy) in relapser patients with HCV hepatitis, genotype 1b. No gain was obtained in prolonging from 6 to 12 months the standard double therapy, while triple therapy with amantadine as an additional regimen for this difficult subgroup of patients showed some cases of SVRs: amantadine addition deserves to be evaluated in larger trials.