Diabetic foot in primary and tertiary (DEFINITE) Care: A health services innovation in coordination of diabetic foot ulcer (DFU) Care within a healthcare cluster - 18-month results from an observational population health cohort study.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional and multi-disciplinary team (MDT) health systems innovation programme at a healthcare cluster in Singapore. We aim to achieve coordinated MDT care across primary and tertiary care for patients with diabetic foot ulcers (DFU), within our public healthcare cluster - an integrated network of seven primary care polyclinics and two acute care tertiary hospitals (1700-bed and 800-bed) with a total catchment population of 2.2 million residents. Results from prospective DEFINITE Care is referenced against a retrospective 2013-2017 cohort, which was previously published. Cardiovascular profile of the study population is compared against the same population's profile in the preceding 12 months. Between June 2020 and December 2021, there were 3475 unique patients with DFU with mean age at 65.9 years, 61.2% male, mean baseline HbA1c at 8.3% with mean diabetes duration at 13.3 years, mean diabetes complication severity index (DCSI) at 5.6 and mean Charlson Comorbidity Index (CCI) at 6.8. In the 12-months preceding enrolment to DEFINITE Care, 35.5% had surgical foot debridement, 21.2% had minor lower extremity amputation (LEA), 7.5% had major LEA whilst 16.8% had revascularisation procedures. At 18-months after the implementation of DEFINITE Care programme, the absolute minor and major amputation rates were 8.7% (n = 302) and 5.1% (n = 176), respectively, equating to a minor and major LEA per 100000 population at 13.7 and 8.0, respectively. This represents an 80% reduction in minor amputation rates (P < .001) and a 35% reduction in major amputation rates (P = .005) when referenced against a retrospective 2013-2017 cohort, which had minor and major LEA per 100000 population at 68.9 and 12.4, respectively. As compared to the preceding 12 months, there was also a significant improvement in cardiovascular profile (glycemic and lipid control) within the DEFINITE population, with improved mean HbAc1 (7.9% from 8.4%, P < .001), low-density lipoprotein (LDL) levels (2.1 mmol/L from 2.2, P < .001), total cholesterol (3.9 mmol/L from 4.1, P < .001) and triglycerides levels (1.6 mmol/L from 1.8, P = .002). Multivariate analysis revealed a history of minor amputation in the preceding 12 months to be an independent predictor for major and minor amputation within the study period of 18 months (Hazard Ratio 3.4 and 1.8, respectively, P < .001). In conclusion, within DEFINITE care, 18-month data showed a significant reduction of minor and major LEA rates, with improved medical optimisation and cardiovascular profile within the study population.

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case-control study.

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case-control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow-up (33% vs 76%, P < .001), decrease in 1-year minor amputation rate (14% vs 3%, P = .007), and decrease in 1-year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.

Diabetes predicts severity of COVID-19 infection in a retrospective cohort: A mediatory role of the inflammatory biomarker C-reactive protein.

Diabetes is a risk factor for developing severe COVID-19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID-19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID-19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%-6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID-19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID-19 outcome was analyzed by cox regression. Adjusted mediation analysis of C-reactive protein (CRP) on the relationship between diabetes and severe COVID-19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID-19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID-19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54-17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92-8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22-4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID-19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID-19 infection, confirming that inflammation is important in the pathogenesis of severe COVID-19 in diabetes.

Obesity is Associated with Poor Covid-19 Outcomes: A Systematic Review and Meta-Analysis.

Our aim was to assess the association between obesity and the risk of unfavourable outcomes (composite of severe disease and mortality) in inpatients with COVID-19. We conducted a systematic search of databases between December 2019 and 28th June 2020. Studies were included if they reported or allowed estimation of an odds ratio (OR) for unfavourable outcome in obese compared to non-obese patients hospitalised for COVID-19. Twenty cohort studies of 28 355 hospitalised patients with COVID-19 infection were included. Meta-analysis estimated a pooled OR of 2.02 (1.41-2.89, p<0.001) for an unfavourable outcome in obese versus non-obese patients when adjusted for age, sex and co-morbidities. When unadjusted for confounders, the OR for unfavourable outcomes was 1.25 (CI 1.07-1.45, p=0.005). An increased adjusted OR was also seen for death (OR 1.51; CI 1.13-2.21, p=0.006) and severe illness (OR 2.26; CI 1.47-3.48, p<0.001). Compared to a normal BMI, the risk of an unfavourable outcome was increased even in overweight patients, with severe obesity having an escalated risk.Obesity is independently associated with an unfavourable outcome of COVID-19 illness, with obese patients having twice the risk of a composite outcome of severe disease or mortality, and a 50% increased risk of death.

Are Adequate Vitamin D Levels Helpful in Fighting COVID-19? A Look at the Evidence.

COVID-19 is a global pandemic with high mortality in vulnerable groups. Given the current lack of definitive treatment or vaccine that significantly reduces mortality rate, governments, researchers and healthcare providers are racing to find possible solutions to the crisis. Vitamin D and its analogues have been previously studied for their non-skeletal benefits. In particular, questions regarding their role in the modulation of immunity have re-surfaced, in view of possible epidemiological links observed between COVID-19 and vitamin D levels in selected populations. In this review, we highlight potential mechanisms and summarise the evidence for and against the potential role of vitamin D supplementation in our fight against COVID-19.

Exposure to a high dose of amoxicillin causes behavioral changes and oxidative stress in young zebrafish.

Autistic spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders characterized by impaired social and communication skills. Autism is widely described as a behavioral syndrome with multiple etiologies where may exhibit neurobiological, genetic, and psychological deficits. Studies have indicated that long term use of antibiotics can alter the intestinal flora followed by neuroendocrine changes, leading to behavioral changes. Indeed, previous studies demonstrate that a high dose of amoxicillin can change behavioral parameters in murine animal models. The objective was to evaluate behavioral and oxidative stress parameters in zebrafish exposed to a high dose of amoxicillin for 7 days. Young zebrafish were exposed to a daily concentration of amoxicillin (100 mg/L) for 7 days. Subsequently, the behavioral analysis was performed, and the brain content was dissected for the evaluation of oxidative stress parameters. Zebrafish exposed to a high dose of amoxicillin showed locomotor alteration and decreased social interaction behavior. In addition, besides the significant decrease of sulfhydryl content, there was a marked decrease in catalase activity, as well as an increased superoxide dismutase activity in brain tissue. Thus, through the zebrafish model was possible to note a central effect related to the exposition of amoxicillin, the same as observed in murine models. Further, the present data reinforce the relation of the gut-brain-axis and the use of zebrafish as a useful tool to investigate new therapies for autistic traits.

Risk factors and clinical profile of autism spectrum disorder in southern Brazil.

In Brazil, as in other countries, it is expected a significant variation of epidemiological and clinical characteristics among individuals with autism spectrum disorder (ASD). This study was performed to explore maternal risk factors and clinical characteristics of children with ASD in a population located in southern Brazil. Data were collected from medical records and analyzed to explore biomarkers associated with ASD. Out of 321 children with ASD, 86.5% were males with a male-to-female ratio of 5.7:1, 50.7% were mild/moderate while 49.3% presented severe ASD. Between the risk factors investigated, gestational infection was significantly associated with severe ASD patients. There was also an association between epilepsy and severe autism. Several gastrointestinal (GI) symptoms were significantly associated with severe ASD. Obesity, followed by lower levels of cholesterol, were also significant factors associated with an ASD diagnosis when compared to age-matched controls. Finally, severe ASD was associated with significantly higher serum serotonin levels when compared to age-matched controls and mild/moderate ASD cases. Our findings demonstrate that our population shares many features associated with ASD around the world, such as GI symptoms, epilepsy, and high serotonin levels. It is worth highlighting the low cholesterol levels associated with obesity as an unusual feature that deserves more attention.

Rapid Access From Primary Care to a Multidisciplinary Clinic at Tertiary Care Improves Clinical Outcomes for Patients With Diabetic Foot Ulcers: Results From Diabetic Foot in Primary and Tertiary (DEFINITE) Care's Lower Extremity Amputation Prevention Program (LEAPP) Clinic.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional, multidisciplinary team (MDT) program for patients with diabetic foot ulcers (DFU) within a healthcare cluster in Singapore. This is one of our subgroup analyses within DEFINITE Care, assessing clinical outcomes of lower extremity amputation prevention program (LEAPP), a multidisciplinary diabetic foot clinic, and non-LEAPP patients within the program. From June 2020 to June 2022, 2798 patients within the DEFINITE cohort completed a minimum of 12-month follow up. Of these patients, 20.6% were managed by LEAPP, whereas 79.4% were non-LEAPP patients. Patients in the LEAPP cohort were older with co-existing metabolic conditions and complications of diabetes. Using non-LEAPP cohort as the reference group and after adjusting for age, gender, ethnicity, comorbidities, and medications, there was a significantly lower risk of death (odds ratio [OR] 0.60, P = .001) and composite major lower extremity amputation (LEA) or death (OR 0.66, P = .002) among LEAPP patients at 1 year with longer mean days from enrollment to minor LEA, major LEA, and death. The adjusted 1-year healthcare utilization outcomes for LEAPP patients demonstrated an increase in inpatient admissions, primary care polyclinic visits, hospital specialist outpatient clinic (SOC) visits and elective day surgery procedures. Despite the increased in inpatients admissions, cumulative hospital length of stay in LEAPP patients were lower. This subgroup analysis has demonstrated that the MDT approach to caring for patients with DFU in tertiary centers not only improves mortality by 40%, but also delayed the incidence of minor LEA, major LEA, and death.

Psychiatric symptoms may contribute to poor quality of life in adolescents with migraine.

BACKGROUND: The impact of migraine on quality of life (QOL) can be aggravated by other comorbid factors. The aim of the present study was to assess the differences in the QOL of adolescents with chronic migraine, episodic migraine, and healthy adolescents, and whether the differences in QOL among the diagnostic groups were associated with the presence of self-reported psychiatric symptoms, such as depression and anxiety. METHODS: A total of 157 adolescents (aged 15-19 years old) were included in the study. Fifty patients had episodic migraine, 56 patients suffered from chronic migraine, and 51 healthy adolescents were controls. All of the participants responded to a detailed headache questionnaire, the Medical Outcomes Trust 36-Item Short-form Health Survey, the State-Trait Anxiety Inventory and the Beck Depression Inventory. RESULTS: Chronic migraine patients showed a significantly lower QOL than the control subjects in five dimensions of the Medical Outcomes Trust 36-Item Short-form Health Survey, and lower QOL than the episodic migraine patients in four dimensions. High levels of self-reported depressive symptoms were associated with lower QOL in five dimensions and high levels of self-reported anxiety were associated with lower QOL in four dimensions. CONCLUSIONS: The QOL of adolescent migraine sufferers may be aggravated not only by migraine but also by other factors, such as anxiety and depressive symptoms, which may contribute to the poor QOL in adolescents suffering from migraine.

Revascularisation Options for Chronic Limb Threatening Ischaemia in Diabetes: Implications From Two Recent Trials.

Chronic limb-threatening ischaemia (CLTI) is a severe form of peripheral arterial disease (PAD) and is associated with an increased risk of amputation, mortality, and significantly impaired quality of life. International guidelines recommend considering timely revascularisation and optimal medical therapy to improve limb perfusion in individuals with CLTI. The 2 primary revascularization approaches for CLTI are open bypass surgery (BS) and endovascular therapy (EV), however, there is currently no consensus on the best initial treatment strategy for CLTI, leading to uncertainty among clinicians. To shed light on this issue, 2 recent trials, namely best endovascular versus best surgical therapy in patients with CLI (BEST-CLI) and bypass versus angioplasty for severe ischaemia of the leg (BASIL-2), have tried to provide valuable insights. While a definitive conclusion on the optimal revascularisation approach is still pending, these trials offer immediate and clinically relevant information to the diabetic foot multidisciplinary team. The trials encompassed a distinct range of patient cohorts and included participants with varying degrees of medical and physical frailty. Taken together, their findings, highlight the need for an individualised revascularisation strategy which accounts for underlying comorbidities, risk factors, disease severity, availability of suitable bypass conduits, surgical risks, and timely access to procedures. Regardless of the chosen strategy, early referral of patients with diabetes and CLTI to a specialist team within a multidisciplinary environment is crucial. Comprehensive care should encompass essential elements such as adequate debridement, infection control, offloading, glycaemic control, smoking cessation, and patient education. By addressing these aspects, healthcare providers can optimise the management and outcomes for individuals with CLTI and diabetes.

Cholesterol metabolism pathway in autism spectrum disorder: From animal models to clinical observations.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a persistent impairment of social skills, including aspects of perception, interpretation, and response, combined with restricted and repetitive behavior. ASD is a complex and multifactorial condition, and its etiology could be attributed to genetic and environmental factors. Despite numerous clinical and experimental studies, no etiological factor, biomarker, and specific model of transmission have been consistently associated with ASD. However, an imbalance in cholesterol levels has been observed in many patients, more specifically, a condition of hypocholesterolemia, which seems to be shared between ASD and ASD-related genetic syndromes such as fragile X syndrome (FXS), Rett syndrome (RS), and Smith- Lemli-Opitz (SLO). Furthermore, it is known that alterations in cholesterol levels lead to neuroinflammation, oxidative stress, impaired myelination and synaptogenesis. Thus, the aim of this review is to discuss the cholesterol metabolic pathways in the ASD context, as well as in genetic syndromes related to ASD, through clinical observations and animal models. In fact, SLO, FXS, and RS patients display early behavioral markers of ASD followed by cholesterol disturbances. Several studies have demonstrated the role of cholesterol in psychiatric conditions and how its levels modulate brain neurodevelopment. This review suggests an important relationship between ASD pathology and cholesterol metabolism impairment; thus, some strategies could be raised - at clinical and pre-clinical levels - to explore whether cholesterol metabolism disturbance has a generally adverse effect in exacerbating the symptoms of ASD patients.

Nocturnal enuresis antecedent is common in adolescents with migraine.

BACKGROUND: Migraine and nocturnal enuresis are highly prevalent disorders with striking similarities. Both have unknown pathophysiology and are considered multifactorial, with neurobiological, genetic, and behavioral aspects involved. Interestingly, the same neurological structures thought to be involved in the pathogenesis of migraine are also thought to be involved in nocturnal enuresis. Few studies, however, have addressed these conditions as related. The aim of this study was to evaluate the antecedent of nocturnal enuresis in a large consecutive series of adolescents with migraine as compared to controls. METHODS: A total of 151 subjects were evaluated; 50 had episodic migraine, 50 had chronic migraine, and 51 were control subjects. All patients were submitted to a detailed questionnaire addressing epidemiological and clinical aspects. RESULTS: There was a strong correlation between the clinical history of nocturnal enuresis and the diagnosis of migraine. CONCLUSION: Our study showed that nocturnal enuresis is a precursor of migraine and a migraine comorbid condition. These results support a pathophysiological linkage between the two conditions.

Social anxiety score is high in adolescents with chronic migraine.

BACKGROUND: Social anxiety disorder, also known as social phobia, is a marked and persistent fear of one or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others. It usually begins in mid-adolescence and has a chronic course and interferes in academic, social, family and personal functioning. Recent studies have shown that social anxiety disorder is more prevalent in adults with migraine. Little evidence on this subject is available for the adolescent population. METHODS: This study was performed between August 2009 and August 2010; all patients were recruited in schools, pediatric or neuropediatric facilities, and were submitted to a detailed headache questionnaire, which consisted of demographic and clinical data. To evaluate social anxiety, the Social Phobia Inventory was used. RESULTS: A total of 151 subjects were evaluated: 50 had chronic migraine, 50 had episodic migraine and 51 were control subjects. In the chronic migraine group, the mean score in the Social Phobia Inventory was 18.5 ± 12.4, which was significantly higher than in the episodic migraine group (12.1 ± 8.1) and in the control group (13.8 ± 10.8; F(2131) = 4.8, P= 0.010). The mean score, however, was not significantly different between the control and episodic migraine groups. CONCLUSIONS: Chronic migraine is strongly associated with high social anxiety score, regardless of demographic data and pain intensity. The total burden of migraine may be increased with social anxiety disorder comorbidity.

Spontaneous periodic hypothermia and hyperhidrosis: a possibly novel cerebral neurotransmitter disorder.

Spontaneous periodic episodes of hypothermia still defy medical knowledge. In 1969, Shapiro et al. described the first two cases of spontaneous periodic hypothermia associated with agenesis of the corpus callosum. Recently, Dundar et al. reported a case of spontaneous periodic hypothermia and hyperhidrosis without corpus callosum agenesis, suggesting that the periodic episodes of hypothermia might be of epileptiform origin. Here we describe two paediatric patients with spontaneous periodic hypothermia without corpus callosum agenesis and demonstrate, to our knowledge for the first time, altered levels of neurotransmitter metabolites within the cerebrospinal fluid.

Sex-related patterns of the gut-microbiota-brain axis in the neuropsychiatric conditions.

Sex differences are often observed in psychiatric patients, especially major depressive disorders (MDD), schizophrenia, and developmental disorders, including autism spectrum disorders (ASDs). The prevalence rates between males and females seem variate according to the clinical condition. Although the findings are still incipient, it is suggested that these differences can involve neuroanatomical, neurochemical, and physiological sex differences. In this context, the microbiota-gut-brain axis hypothesis arises to explain some aspects of the complex pathophysiology of neuropsychiatric disorders. The microbiota composition is host-specific and can change conforming to age, sex, diet, medication, exercise, and others. The communication between the brain and the gut is bidirectional and may impact the entire system homeostasis. Many pathways appear to be involved, including neuroanatomic communication, neuroendocrine pathways, immune system, bacteria-derived metabolites, hormones, neurotransmitters, and neurotrophic factors. Although the clinical and preclinical studies are sparse and not very consistent, they suggest that sex differences in the gut microbiota may play an essential role in some neuropsychiatric conditions. Thus, this narrative review has as a mainly aim to show the points sex-related patterns associated to the gut-microbiota-brain axis in the MDD, ASDs, and schizophrenia.

Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities.

OBJECTIVE: To assess urinary 6-sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls. BACKGROUND: Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders. METHODS: Urine samples were collected into a single plastic container over a 12-hour period from 8:00 pm to 8:00 am of the next day, and 6-sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory. RESULTS: A total of 220 subjects were evaluated - 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6-sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6-sulphatoxymelatonin levels and depression, anxiety, and fatigue. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.

Autism associated with 12q (12q24.31-q24.33) deletion: further report of an exceedingly rare disorder.

Chromosomal abnormalities are responsible for several congenital malformations in the world, some of these are associated to telomeric/subtelomeric deletions. The abnormalities involving the telomere of chromosome 12 are rare, with few reports of deletions involving 12q24.31 region in the literature, and, to our knowledge, only four of them in the 12q24.31-q24.33 region. We report a further case of interstitial deletion of bands 12q24.31-q24.33 associated with autism spectrum disorder. A 2-year-old boy with global developmental delay associated with multiple congenital anomalies. The Human Genome CGH Microarray 60K confirmed the diagnosis of 12q deletion syndrome. This study made a review of the current literature comparing our patient with previously reported cases. These detailed analyses contribute to the development of genotype/phenotype correlations for 12q deletions that will aid in better diagnosis and prognosis of this deletion.

Attention Deficit Disorder with Hyperactivity Symptoms in Early-Treated Phenylketonuria Patients.

SECTION TITLE: Objectives To assess the presence of symptoms consistent with Attention Deficit Disorder with Hyperactivity (ADHD) in all patients with early-treated phenylketonuria (PKU) in the State of Santa Catarina in southern Brazil. MATERIALS & METHODS: All of the patients diagnosed with PKU by newborn-screening tests, with ages varying from 6 to 18 years and who started treatment before 60 days of life and presented phenylalanine levels consistently below 6 mg/dL throughout treatment, were included. The subjects were invited to complete a questionnaire that collected sociodemographic, gestational and clinical data. ADHD symptoms were assessed using the revision of the Swanson, Nolan and Pelham Questionnaire. RESULTS: A total of 34 patients were evaluated, who were 53% male and 94% white and had an average age of 12 years, and 15% were born premature. According to the Swanson, Nolan and Pelham Questionnaire, 13 patients (38%) met the diagnostic criteria for ADHD, with 2 patients having the inattentive type, 6 patients having the hyperactive or impulsive type and 1 patient having the oppositional defiant disorder type. CONCLUSION: Although the patients with PKU were regularly treated from birth, there was a high prevalence of symptoms consistent with ADHD. A pathophysiological interface that involves the dopamine metabolic pathway may exist between the two conditions.

Magnetic resonance spectroscopy reveals an epileptic network in juvenile myoclonic epilepsy.

PURPOSE: To investigate the cerebral metabolic differences between patients with juvenile myoclonic epilepsy (JME) and normal controls and to evaluate to what extent these metabolic alterations reflect involvement of an epileptic network. METHODS: Sixty patients with JME were submitted to multi-voxel proton spectroscopy (1H-MRS) at 1.5 T over medial prefrontal cortex (MPC), primary motor cortex (PMC), thalamus, striatum, posterior cingulate gyrus (PCG), and insular, parietal, and occipital cortices. We determined ratios for integral values of N-acetyl-aspartate (NAA) and glutamate-glutamine (GLX) over creatine-phosphocreatine (Cr). The control group (CTL) consisted of 30 age- and sex-matched healthy volunteers. RESULTS: The NAA/Cr ratio, a measure of neuronal injury, was reduced in PMC, MPC, and thalamus among patients. In addition, they had an altered GLX/Cr ratio, which is involved in excitatory activity, on PMC, MPC, and PCG, where it was reduced, whereas it was increased on insula and striatum. Multiple regression analysis revealed the strongest correlation between thalamus and MPC, but the thalamus was also correlated with insula, occipital cortex, and striatum among patients. Lower NAA/Cr was observed with advancing age and duration of epilepsy, regardless of frequency of seizures and antiepileptic drug therapy in thalamus and frontal cortex. DISCUSSION: The identification of a specific network of neurochemical dysfunction in patients with JME, with diverse involvement of particular structures within the thalamocortical circuitry, suggests that cortical hyperexcitability in JME is not necessarily diffuse, supporting the knowledge that the focal/generalized distinction of epileptogenesis should be reconsidered. Furthermore, evidence is provided toward progressive neuronal dysfunction in JME.

Are personality traits of juvenile myoclonic epilepsy related to frontal lobe dysfunctions? A proton MRS study.

PURPOSE: Personality traits characterized by emotional instability and immaturity, unsteadiness, lack of discipline, hedonism, frequent and rapid mood changes, and indifference toward one's disease have been associated with patients who have juvenile myoclonic epilepsy (JME). Literature data demonstrate worse seizure control and more psychosocial dysfunctions among patients with JME who have those traits. In this controlled study we performed a correlation analysis of psychiatric scores with magnetic resonance spectroscopy (MRS) values across JME patients, aiming to verify the existence of a possible relation between frontal lobe dysfunction and the prevalence of personality disorders (PDs) in JME. METHODS: Sixteen JME patients with cluster B PDs, 41 JME patients without any psychiatric disorder, and 30 healthy controls were submitted to a psychiatric evaluation and to a quantitative multivoxel MRS of thalamus; insula; cingulate gyrus; striatum; and frontal, parietal, and occipital lobes. Groups were homogeneous according to age, gender, and manual dominance. Psychiatric evaluation was performed through the Scheduled Clinical Interview for DSM-IV, Axis I and II (SCID I and II, respectively). RESULTS: A significant reduction of N-acetyl-aspartate over creatinine (NAA/Cr) ratio was observed mainly in the left frontal lobe in the JME and PD group. In addition, a significant increase in the glutamate-glutamine over creatinine GLX/Cr ratio was also observed in this referred region in the same group. DISCUSSION: These data support the hypothesis that PDs in JME could represent neuronal dysfunction and possibly a more severe form of this epileptic syndrome.