A DM1 family with interruptions associated with atypical symptoms and late onset but not with a milder phenotype.

Carriage of interruptions in CTG repeats of the myotonic dystrophy protein kinase gene has been associated with a broad spectrum of myotonic dystrophy type 1 (DM1) phenotypes, mostly mild. However, the data available on interrupted DM1 patients and their phenotype are scarce. We studied 49 Spanish DM1 patients, whose clinical phenotype was evaluated in depth. Blood DNA was obtained and analyzed through triplet-primed polymerase chain reaction (PCR), long PCR-Southern blot, small pool PCR, AciI digestion, and sequencing. Five patients of our registry (10%), belonging to the same family, carried CCG interruptions at the 3'-end of the CTG expansion. Some of them presented atypical traits such as very late onset of symptoms ( > 50 years) and a severe axial and proximal weakness requiring walking assistance. They also showed classic DM1 symptoms including cardiac and respiratory dysfunction, which were severe in some of them. Sizes and interrupted allele patterns were determined, and we found a contraction and an expansion in two intergenerational transmissions. Our study contributes to the observation that DM1 patients carrying interruptions present with atypical clinical features that can make DM1 diagnosis difficult, with a later than expected age of onset and a previously unreported aging-related severe disease manifestation.

Pain treatment and its cost in old people with dementia: a descriptive analysis from the Registry of Dementias of Girona (ReDeGi).

BACKGROUND: Pain prevalence is high among elderly people, and equally prevalent in those with dementia. The aim of this study was to describe the use analgesics, as well as the cost of these treatments in old people with dementia. METHODS: We used a cross-sectional design using 1186 cases registered by the Registry of Dementias of Girona from 2007 to 2008. All drugs were categorized following the Anatomic Therapeutic Chemical classification and grouped according to the World Health Organization (WHO) analgesic ladder steps. Descriptive statistical methods were used. RESULTS: Analgesics were prescribed to 78.6% (95% CI, 76.2-81.0) of the registered cases. Of them, 80.6% (95% CI, 78.0-83.2) were treated following step 1 of the WHO analgesic ladder, 16.8% (95% CI, 14.4-19.3) following step 2 and 2.6% (95% CI, 1.5-3.6) following step 3. Pain treatment in old people with dementia had a cost of 42.1 € per patient and year, with no significant differences depending on the subtype of dementia. CONCLUSIONS: The use of analgesics in our sample was not associated to age or to dementia severity, which are themselves risk factors for increased pain. Moreover, no differences were detected depending on the subtype of dementia.

Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs.

PURPOSE: To investigate the efficacy and tolerability of perampanel (PER) when administered as a first add-on therapy to patients with focal epilepsy or idiopathic generalized epilepsy (IGE) taking one other antiseizure drug (ASD). METHODS: This multicentre, retrospective, one-year observational study collected data from patients (≥12 years) who initiated treatment with PER as first add-on therapy. Patients had to be experiencing inadequate seizure control on ASD monotherapy and tried ≤3 ASD monotherapies before initiating PER. Multivariate logistic regression analyses were performed, adjusted for the number and type of previous seizures, duration and aetiology of epilepsy. RESULTS: Of the 149 patients included in the study (mean age 41 years; 54.4 % male), 118 (79.2 %) were still receiving PER as first add-on treatment after 12 months. Mean PER dose was 6.2 mg/day. At 12 months, 45.6 % were seizure-free and 84.6 % responders. A significant difference in seizure freedom rate was found between patients with IGE and patients with focal epilepsy, but not in responders. Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs; conversely, increased seizure control was seen when the same dose of PER was combined with enzyme-inhibiting ASDs. The most frequent adverse events were dizziness (15.4 %), irritability (14.1 %) and drowsiness (14.1 %); no differences in tolerance were observed among different combinations. CONCLUSION: PER demonstrated a good efficacy and safety profile when used as a first add-on therapy in patients who did not respond to monotherapy. PER dose adjustments may optimize seizure control when combined with strong enzyme-inducing or enzyme-inhibiting ASDs.