Self-reported outcomes and quality of life of patients with non-dystrophic myotonia: The French IMPACT 2022 survey.

Non-dystrophic myotonias (NDM) are disabling genetic diseases that impact quality of life. To reduce the impact of NDM, patients develop coping strategies such as lifestyle adaptation and avoiding key triggers. To understand how myotonia affects patients' lives, the IMPACT survey, an online questionnaire on patient-reported outcomes, was developed based on international IMPACT questionnaire. The French IMPACT 2022 survey was completed by 47 NDM French patients. Besides muscle stiffness (98%), patients reported muscle pain (83%), falls (70%) and anxiety (77%). These issues negatively impacted abilities to work/study (49%), daily life at home (49%) and overall mobility outside (49%). Most patients (96%) reported ongoing pharmacological treatment (mexiletine, 91%) associated with improvement in muscle stiffness (100%) and reduction in falls (94%), muscle pain (87%) and anxiety (80%). Patients were moderately satisfied (19.1%), satisfied (42.6%) and very satisfied (29.8%) with the current management; 32% rated their quality of life positively (≥ 8 on 10-point scale). In conclusion, this French survey confirms the impact of myotonia on daily life and quality of life. The improvement in patient-reported outcomes in treated participants highlights the importance of managing myotonia with effective treatments. More work should be initiated to assess the importance of NDM symptom management and patients' adherence and compliance to treatment.

Current clinical management of CIDP with immunoglobulins in France: An expert opinion.

Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.

Phenotypical variability and atypical presentations in a French cohort of Andersen-Tawil syndrome.

BACKGROUND AND PURPOSE: Andersen-Tawil syndrome (ATS) is a skeletal muscle channelopathy caused by KCNJ2 mutations, characterized by a clinical triad of periodic paralysis, cardiac arrhythmias and dysmorphism. The muscle phenotype, particularly the atypical forms with prominent permanent weakness or predominantly painful symptoms, remains incompletely characterized. METHODS: A retrospective clinical, histological, electroneuromyography (ENMG) and genetic analysis of molecularly confirmed ATS patients, diagnosed and followed up at neuromuscular reference centers in France, was conducted. RESULTS: Thirty-five patients from 27 unrelated families carrying 17 different missense KCNJ2 mutations (four novel mutations) and a heterozygous KCNJ2 duplication are reported. The typical triad was observed in 42.9% of patients. Cardiac abnormalities were observed in 65.7%: 56.5% asymptomatic and 39.1% requiring antiarrhythmic drugs. 71.4% of patients exhibited dysmorphic features. Muscle symptoms were reported in 85.7%, amongst whom 13.3% had no cardiopathy and 33.3% no dysmorphic features. Periodic paralysis was present in 80% and was significantly more frequent in men. Common triggers were exercise, immobility and carbohydrate-rich diet. Ictal serum potassium concentrations were low in 53.6%. Of the 35 patients, 45.7% had permanent weakness affecting proximal muscles, which was mild and stable or slowly progressive over several decades. Four patients presented with exercise-induced pain and myalgia attacks. Diagnostic delay was 14.4 ± 9.5 years. ENMG long-exercise test performed in 25 patients (71.4%) showed in all a decremental response up to 40%. Muscle biopsy performed in 12 patients revealed tubular aggregates in six patients (associated in two of them with vacuolar lesions), dystrophic features in one patient and non-specific myopathic features in one patient; it was normal in four patients. DISCUSSION: Recognition of atypical features (exercise-induced pain or myalgia and permanent weakness) along with any of the elements of the triad should arouse suspicion. The ENMG long-exercise test has a high diagnostic yield and should be performed. Early diagnosis is of utmost importance to improve disease prognosis.

Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real-life study.

BACKGROUND AND PURPOSE: Fifteen percent of patients with myasthenia gravis (MG) are refractory to conventional treatment. Case reports and a few studies show probable benefit of rituximab in these cases. Our objective was to assess the efficacy and the safety of rituximab in patients with MG, in a multicentric real-life study. METHOD: Inclusion criteria were: age > 18 years; MG with anti-acetylcholine receptor (AChR) antibodies, anti-muscle-specific kinase (MuSk) antibodies or significant decrement after repetitive nerve stimulation; Myasthenia Gravis Foundation of America (MGFA) class >II; refractory or steroid-dependent MG; and treatment with rituximab. Efficacy was assessed at 6 months using the MGFA-post-intervention status (PIS) score, the myasthenic muscle score (MMS) and the number of patients receiving steroids <10 mg/day. Data on adverse events were collected. RESULTS: Twenty-nine patients were included: 20 with anti-AChR MG, five with anti-MuSK MG and four with seronegative MG. MGFA-PIS score was improved or better (improved, minimal manifestations or remission) in 86.2% of patients after 6 months of treatment (P < 0.0001). The mean MMS increased from 68.8 to 83.1 (P < 0.0001). A decrease in steroid dosage (<10 mg/day) was effective in 57.9% of treated patients. In all, 42.8% of patients experienced adverse events: infections (21.4% of patients); infusion reaction (7%); bradycardia (3.7%); and cytopenia (7%). CONCLUSION: The present study demonstrates the efficacy and safety of rituximab in patients with MG. Additional studies remain necessary to determine the role of rituximab in the pharmacopeia of MG treatment and to establish precise recommendations for the infusion protocol.

Exercise testing-based algorithms to diagnose McArdle disease and MAD defects.

OBJECTIVE: As exercise intolerance and exercise-induced myalgia are commonly encountered in metabolic myopathies, functional screening tests are commonly used during the diagnostic work-up. Our objective was to evaluate the accuracy of isometric handgrip test (IHT) and progressive cycle ergometer test (PCET) to identify McArdle disease and myoadenylate deaminase (MAD) deficiency and to propose diagnostic algorithms using exercise-induced lactate and ammonia variations. METHODS: A prospective sample of 46 patients underwent an IHT and a PCET as part of their exercise-induced myalgia and intolerance evaluation. The two diagnostics tests were compared against the results of muscle biopsy and/or the presence of mutations in PYGM. A total of 6 patients had McArdle disease, 5 a complete MAD deficiency (MAD absent), 12 a partial MAD deficiency, and 23 patients had normal muscle biopsy and acylcarnitine profile (disease control). RESULTS: The two functional tests could diagnose all McArdle patients with statistical significance, combining a low lactate variation (IHT: <1 mmol/L, AUC = 0.963, P < .0001; PCET: <1 mmol/L, AUC = 0.990, P < .0001) and a large ammonia variation (IHT: >100 µmol/L, AUC = 0.944, P = .0005; PCET: >20 µmol/L, AUC = 1). PCET was superior to IHT for MAD absent diagnosis, combining very low ammonia variation (<10 µmol/L, AUC = 0.910, P < .0001) and moderate lactate variation (>1 mmol/L). CONCLUSIONS: PCET-based decision tree was more accurate than IHT, with respective generalized squared correlations of 0.796 vs 0.668. IHT and PCET are both interesting diagnostic tools to identify McArdle disease, whereas cycle ergometer exercise is more efficient to diagnose complete MAD deficiency.

Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence.

OBJECTIVE: To investigate possible linkages between neurodevelopmental delay and neurodevelopmental spectrum disorders and exposure to medication with effects on serotonin reuptake inhibition during pregnancy. METHODS: We systematically reviewed the epidemiological literature for studies bearing on this relationship in children born with neurodevelopmental spectrum disorder and related conditions, as well as animal studies giving serotonin reuptake inhibitors to pregnant animals and in addition reviewed the literature for proposals as to possible mechanisms that might link effects on serotonin reuptake with cognitive changes post-partum.The epidemiological studies were analysed to produce Forest plots to illustrate possible relations. RESULTS: The odds ratio of Autistic Spectrum or related Disorders in children born to women taking serotonin reuptake inhibiting antidepressants during pregnancy in case control studies was 1.95 (95% C.I. 1.63, 2.34) and in prospective cohort studies was 1.96 (95% C.I. 1.33, 2.90). CONCLUSIONS: There appears to be a link between serotonin reuptake inhibition in pregnancy and developmental delay and spectrum disorders in infancy leading to cognitive difficulties in childhood. More work needs to be done to establish more precisely the nature of the difficulties and possible mechanisms through which this link might be mediated.

Increasing parental provision and children's consumption of lunchbox fruit and vegetables in Ireland: the Food Dudes intervention.

BACKGROUND/OBJECTIVES: Previous research in the United Kingdom, where there is a school canteen system, has shown that the Food Dudes intervention substantially increases children's fruit and vegetable consumption. The current study evaluated its effectiveness in Ireland where school meals are not provided and children bring food to school in lunchboxes. SUBJECTS/METHODS: Participants were 4- to 11-year-old children attending two primary schools; the schools were randomly assigned to experimental or control conditions (n=228 and 207, respectively). During the 16-day intervention in the experimental school, children watched video adventures featuring the heroic Food Dudes, and received small rewards for eating fruit and vegetables provided. In both schools, parental provision and children's consumption of fruit and vegetables in the lunchboxes were assessed at baseline and 12-month follow-up (Lunchbox measures). Fruit and vegetables were provided in both schools over an 8-day baseline phase and the 16-day intervention, and children's consumption was measured (school-provided food measures). RESULTS: Relative to baseline, consumption of the school-provided foods increased during the intervention in the experimental school (P<0.001), whereas in the control school it showed a significant decline. At 12-month follow-up, parents in the experimental school provided and their children consumed significantly more lunchbox fruit, vegetables and juice relative to baseline and to the control school (P<0.001 in all instances). CONCLUSIONS: The Food Dudes intervention was effective in changing parental provision and children's consumption of lunchbox fruit and vegetables in Ireland.

The incidence and prevalence of manic-melancholic syndromes in North West Wales: 1875-2005.

OBJECTIVE: Against a background of recent interest in the concept of melancholia, we report data on the incidence and prevalence of manic, melancholic and postpartum syndromes from North West Wales. METHOD: We have utilized a database of the complete records of all admission to the North Wales Asylum from 1875 to 1924, and compared the findings for mania, melancholia, and postpartum psychoses from this sample, with admissions for these disorders to the North West Wales mental health services between 1995 and 2005. RESULTS: The incidence of bipolar disorder, as well as melancholia with and without psychotic features appears stable from 1875 to 2005 but there has been a dramatic decline in the incidence of de novo onset psychoses in the postpartum period. The prevalence of admissions for bipolar disorder, and for severe depressive disorders has increased dramatically during this period. CONCLUSION: There are some grounds for revisiting the concept of manic-melancholic disorder put forward by Rafaelsen. The changes in the incidence of postpartum psychoses may have a wider significance for the affective disorders in general.

Postpartum psychosis: two cohorts compared, 1875-1924 and 1994-2005.

BACKGROUND: There has been a long-standing debate as to whether postpartum psychoses are distinct from other psychoses. While the outcomes of postpartum psychosis are in general thought to be good, the disorder is linked to a high rate of suicide. METHOD: We have utilized a database of 3872 admissions to the North Wales Asylum during the period 1875-1924 to extract data on the prevalence, course and clinical features of postpartum psychoses during this period. We have collected first admissions for postpartum psychosis between 1994 and 2005 in North West Wales to establish a current incidence rate for the disorder. RESULTS: The incidence of psychoses with a first onset in the postpartum period in North West Wales has fallen in the modern period, while the incidence of postpartum psychoses in women with a pre-existing mental illness remains the same. Some features of the clinical picture and course of postpartum psychoses differ from other psychoses, but may be gender rather than disorder linked. CONCLUSIONS: These findings suggest that psychoses with their first onset in the postpartum period may be vanishing. If replicated, this would support claims that these disorders are distinct from other disorders. Alternately, if regarded as affective disorders, establishing the basis for the apparent decline in frequency of these disorders may have implications for other affective disorders.

Long-term results (10 years) of a prospective trial comparing Lo-tact-1 monoclonal antibody and anti-thymocyte globulin induction therapy in kidney transplantation.

To evaluate long-term patient and graft survival, and the incidence of acute and chronic rejection, infectious diseases and malignancies following induction therapy with a rat monoclonal interleukin 2 receptor antibody, Lo-Tact-1, or anti-thymocyte globulin (ATG). Forty first-time kidney transplant patients were prospectively randomized to two groups between May 1990 and June 1991. Twenty recipients were treated with Lo-Tact-1 (group 1) and the other 20, with ATG (group 2) during the first 14 days of the transplantation protocol. All patients were treated with azathioprine, steroids and cyclosporin A. Data were collected over 10 years. Median age was 42.1 years in group 1 and 39.3 years in group 2. Six recipients died during the 10 years of follow-up. All had functioning grafts. Death-censored graft survival was 35% in group 1 and 45% in group 2 after 10 years (P = NS). The number of acute rejection was similar in the two groups. Chronic allograft rejection was significantly more frequent in group 2 (n = 9) than in group 1 (n = 3), P < 0.05. Viral and bacterial infections were more frequent in group 2 than in group 1 (respectively 8 vs. 2 and 16 vs. 10, P < 0.05). Three patients had cancer. Although both Lo-tact-1 and ATG effectively prevented acute renal rejection, fewer bacterial and viral infections and cases of chronic allograft rejection were observed in Lo-tact-1-treated patients after 10 years of follow-up, demonstrating the potential value of this treatment for kidney transplantation.

Resistance and susceptibility to weight gain: individual variability in response to a high-fat diet.

An obesigenic environment is a potent force for promoting weight gain. However, not all people exposed to such an environment become obese; some remain lean. This means that some people are susceptible to weight gain (in a weight-promoting environment) and others are resistant. Identifying the characteristics of appetite control and food motivation in these two groups could throw light on the causes of weight gain and how this can be either treated or prevented. We have investigated the issue experimentally by identifying people who habitually consume a high-fat diet (greater than 43% fat energy). These individuals have been termed high-fat phenotypes. We have compared individuals, of the same age (mean=37 years old) and gender (male), who have gained weight (BMI=34) or who have remained lean (BMI=22). The susceptible individuals are characterised by a cluster of characteristics including a weak satiety response to fatty meals, a maintained preference for high-fat over low-energy foods in the post-ingestive satiety period, a strong hedonic attraction to palatable foods and to eating, and high scores on the TFEQ factors of Disinhibition and Hunger. The analysis of large databases suggests that this profile of factors contributes to an average daily positive energy balance from food of approximately 0.5 MJ. This profile of characteristics helps to define the symptomatology of a thrifty phenotype.

Pneumocystis carinii infection: current treatment and prevention.

Pneumocystis carinii is a common cause of pneumonia in individuals who are immunosuppressed by HIV infection. Use of molecular biological techniques show that P. carinii is a fungus and that infection in man is not a zoonosis. Invasive tests such as sputum induction or bronchoscopy are used to make the diagnosis of P. carinii pneumonia. Life long primary prophylaxis is given to HIV positive individuals with CD4+ lymphocyte counts < 0.20 x 10(9)/L or a CD4: total lymphocyte ratio of < 1.5, constitutional symptoms, or with other AIDS defining diseases. Secondary prophylaxis is given after a first episode to prevent a recurrence. First choice for primary and secondary prophylaxis is oral co-trimoxazole 960 mg od or three times a week. In patients who are intolerant to co-trimoxazole, nebulised pentamidine or dapsone (with or without pyrimethamine) are second and third choices. In a patient with acute PCP disease, severity should be assessed using clinical, radiographic and blood gas criteria as those with moderate or severe disease will benefit from adjuvant glucocorticoids. Co-trimoxazole (120 mg/kg/day in divided doses for 21 days) is first choice therapy for PCP of all degrees of severity. In patients who fail to respond to co-trimoxazole or who are intolerant to it, second line treatment is iv pentamidine in those with severe disease and oral dapsone with trimethoprim, oral clindamycin with primaquine or iv pentamidine in those with mild or moderately severe disease.

Cholecystokinin-dopamine interactions within the nucleus accumbens in the control over behaviour by conditioned reinforcement.

Cholecystokinin (CCK) is colocalised with dopamine in the postero-medial nucleus accumbens (NAS). We have utilised an acquisition of a new response procedure to investigate the interaction between CCK and dopamine in the control over behaviour by conditioned reinforcers. A conditioned reinforcer (CR) may be defined as an initially neutral stimulus which gains control over behaviour through selective association with a primary reinforcer. Here, rats learned to associate a light/noise compound stimulus with the imminent availability of 10% sucrose reinforcement. Later, in the absence of sucrose, responding on one of two novel levers (the CR lever) was acquired and maintained by contingent presentation of the CR alone, while responding on the second lever had no programmed consequences. In Expt. 1, infusion of 10 micrograms D-amphetamine within the postero-medial NAS enhanced responding selectively on the CR lever. Infusion of sulphated CCK octapeptide (CCK: 1 or 10 ng) alone within the same area had no effect on response rate. However, infusion of CCK immediately prior to D-amphetamine caused a dose-dependent potentiation of the impact of D-amphetamine upon rates of response on the CR lever. In Expt. 2, infusion of D-amphetamine (10 micrograms) within the postero-medial NAS again enhanced responding selectively upon the CR lever. Intra-accumbens infusion of CCK (10 ng), or s.c. administration of the CCKA receptor antagonist devazepide had no effect upon response rates. However, CCK again potentiated the D-amphetamine-induced increase in rates of response, and this potentiation was blocked by pretreatment with devazepide. These results are discussed in terms of the co-modulation by CCK and dopamine of the processing of reward-related stimuli within the NAS.

Antibody response after influenza immunization with various vaccine doses: a double-blind, placebo-controlled, multi-centre, dose-response study in elderly nursing-home residents and young volunteers.

The dose effect (0, 10, 20 and 60 micrograms) of influenza subunit vaccine on the antibody response was investigated in nursing-home residents and young controls. The vaccine antigens were: A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and B/Beijing/1/87. For the influenza B antigen, the post-GMT and the 'percentage protective titre' increased significantly both in the young controls and nursing-home residents. No dose effect was observed for the A/Taiwan, and a minor dose effect for A/Sichuan. All vaccine doses were well tolerated by both groups. We conclude from our data that higher vaccine doses may result in a better antibody response against some antigens but not against others. Therefore, in general, increasing the vaccine dose is no adequate method to improve the antibody response.

Prophylactic use of the IL-2 receptor-specific monoclonal antibody LO-Tact-1 with cyclosporin A and steroids in renal transplantation.

LO-Tact-1 is a rat anti-human monoclonal antibody which is directed to the 55-kDa alpha-chain of the interleukin 2 (IL2) receptor. We conducted a pilot trial in 15 first-time cadaveric renal transplant patients undergoing for immunosuppression a 14-day course of LO-Tact-1 (10 mg i.v. daily) together with cyclosporine, low dose steroids (0.5 mg/kg) and azathioprine. Results showed a good immunosuppressive effect, as measured by the similar incidence of acute rejection episodes (0.6 per patient) when compared with 20 patients treated during the same period with our standard quadruple prophylactic combination with higher initial doses of steroids (2 mg/kg) and antilymphocyte globulin (ALG) instead of LO-Tact-1 (0.4 per patient). At 2 years post-transplant, graft survival was 93%, and only 1 patient lost his kidney by rejection. No local or general adverse effect of antibody administration was encountered, and haematological changes remained of minor importance. Local bacterial infection was observed in 3 patients, but viral diseases (including cytomegalovirus, CMV) remained exceptional. In contrast, severe clinical CMV infections occurred in 3 patients (15%) treated by ALG. Nine of 15 patients developed rat-specific antibodies, but only 4 before the completion of LO-Tact-1 treatment, without any correlation with the further development of acute rejection. Patients who suffered rejection had lower LO-Tact-1 levels and higher soluble IL2 receptor levels during the period of infusion, suggesting the crucial importance of pharmacokinetic monitoring to adjust individual doses.

[Treatment with Lo-Tact-1, a monoclonal antibody to the interleukin-2 receptor, in kidney transplantation]. / Traitement par l'anticorps monoclonal anti-récepteur de l'interleukine 2 Lo-Tact-1 en transplantation rénale.

From May to August 1989 15 cadaver-donor renal transplant recipients were treated for 14 days with LO-Tact-1 (10 mg i.v. per day) in combination with cyclosporin (8 mg/kg/day from day-1), low-dose steroids (1/2 mg/kg/day from day 1, then reduced to 0.25 mg/kg at day 26 and 10 mg/day at day 45), and azathioprine (1 mg/kg/day) started at day 45. LO-Tact-1 is a rat monoclonal antibody which is directed to the interleukin-2 receptor. The control group consisted of 20 patients receiving cyclosporin, high-dose steroids (2 mg/day at day 1) and a 14-day course of polyclonal horse antilymphocyte globulins (ALG). Seven patients experienced 9 rejections during the first 3 months post-transplant between day 10 and day 67 (mean 0.6 per patient), comparable to the incidence of rejections in the control group: 8 rejections in 7 patients (mean 0.4 per patient). All rejections were reversed by steroid boluses and ATG. To date, all study patients have functioning grafts, and at 1-year post-transplant, the mean blood creatinine level is 161.2 mumol/l. In the control group, one patient died of CMV infection, and 2 other grafts failed due to rejection. No adverse effect of antibody administration was observed, and hematological changes remained of minor importance. Viral infections were not observed, except one case of herpes simplex. Comparatively, clinical CMV infections occurred in 3 patients receiving ALG (15 percent). Our data suggest that a combination anti-IL-2 monoclonal antibody, cyclosporin and low-dose steroids can safely be administered to allograft recipients, avoid severe viral infections, and, in our early experience, is as potent as the powerful combination ALG, cyclosporin and high-doses steroids in preventing allograft rejection.

Comparative three-month study of the efficacies of metformin and gliclazide in the treatment of NIDD.

In order to compare the effects of metformin and gliclazide on fasting serum insulin, 60 non-insulin dependent diabetics were included in a multi-centre study. Patients on a diabetic diet alone or a diabetic diet together with a sulphonylurea hypoglycaemic agent, with a fasting glucose greater than 1.4 g/l, on two measurements were included in the study. They were randomly allocated to two parallel groups and received either gliclazide or metformin. They were treated for three months and attended for consultation at one month and three months. The fasting serum insulin level decreased significantly in the group receiving metformin (26.2 +/- 3.2 mlU/L at entry versus 19.8 +/- 2.3 mlU/L after three months: less than 0.01), and increased in a non-significant way in the group receiving gliclazide (21.6 +/- 3 mlU/L versus 26.5 +/- 5 mlU/L after three months: NS). The difference between the two groups was significant (p less than 0.01). There was a comparable significant improvement in blood sugar levels during the three months in both patients receiving gliclazide and metformin. However, significant weight loss (p less than 0.05) occurred only in patients receiving metformin. There was an identical improvement in blood sugar control in both patients receiving gliclazide and metformin over the three months. On the other hand, fasting serum insulin levels decreased significantly in patients receiving metformin compared to gliclazide. The effect of metformin on serum insulin levels is probably due to its action on insulin resistance and its lack of effect on insulin secretion, in contrast to sulphonylurea hypoglycaemic agents like gliclazide.