Tongue weakness and atrophy differentiates late-onset Pompe disease from other forms of acquired/hereditary myopathy.

Late-onset Pompe disease (LOPD) is an inherited autosomal recessive progressive metabolic myopathy that presents in the first year of life to adulthood. Clinical presentation is heterogeneous, differential diagnosis is challenging, and diagnostic delay is common. One challenge to differential diagnosis is the overlap of clinical features with those encountered in other forms of acquired/hereditary myopathy. Tongue weakness and imaging abnormalities are increasingly recognized in LOPD. In order to explore the diagnostic potential of tongue involvement in LOPD, we assessed tongue structure and function in 70 subjects, including 10 with LOPD naive to treatment, 30 with other acquired/hereditary myopathy, and 30 controls with neuropathy. Tongue strength was assessed with both manual and quantitative muscle testing. Ultrasound (US) was used to assess tongue overall appearance, echointensity, and thickness. Differences in tongue strength, qualitative appearance, echointensity, and thickness between LOPD subjects and neuropathic controls were statistically significant. Greater tongue involvement was observed in LOPD subjects compared to those with other acquired/hereditary myopathies, based on statistically significant decreases in quantitative tongue strength and sonographic muscle thickness. These findings provide additional evidence for tongue involvement in LOPD characterized by weakness and sonographic abnormalities suggestive of fibrofatty replacement and atrophy. Findings of quantitative tongue weakness and/or atrophy may aid differentiation of LOPD from other acquired/hereditary myopathies. Additionally, our experiences in this study reveal US to be an effective, efficient imaging modality to allow quantitative assessment of the lingual musculature at the point of care.

Consensus recommendations for the classification and long-term follow up of infants who screen positive for Krabbe Disease.

OBJECTIVE: To provide updated evidence and consensus-based recommendations for the classification of individuals who screen positive for Krabbe Disease (KD) and recommendations for long-term follow-up for those who are at risk for late onset Krabbe Disease (LOKD). METHODS: KD experts (KD NBS Council) met between July 2017 and June 2020 to develop consensus-based classification and follow-up recommendations. The resulting newly proposed recommendations were assessed in a historical cohort of 47 newborns from New York State who were originally classified at moderate or high risk for LOKD. RESULTS: Infants identified by newborn screening with possible KD should enter one of three clinical follow-up pathways (Early infantile KD, at-risk for LOKD, or unaffected), based on galactocerebrosidase (GALC) activity, psychosine concentration, and GALC genotype. Patients considered at-risk for LOKD based on low GALC activity and an intermediate psychosine concentration are further split into a high-risk or low-risk follow-up pathway based on genotype. Review of the historical New York State cohort found that the updated follow-up recommendations would reduce follow up testing by 88%. CONCLUSION: The KD NBS Council has presented updated consensus recommendations for efficient and effective classification and follow-up of NBS positive patients with a focus on long-term follow-up of those at-risk for LOKD.

Sturge-Weber syndrome presenting in late adulthood.

A 75-year-old woman presents to the acute medical take with confusion and headache following a road traffic accident. She had previously been fit and well, living alone with no assistance. Following multiple investigations, she was diagnosed with Sturge-Weber Syndrome, a rare neurocutaneous disorder that usually presents with seizures in childhood. This case highlights an unusual example of this syndrome, presenting for the first time later in life.

A 48-Year-Old Woman With Chronic Cough, Dyspnea, and Bronchiectasis.

CASE PRESENTATION: A 48-year-old woman sought a second opinion for dyspnea and chronic productive cough; she was a never smoker. Mild respiratory symptoms persisted since childhood and had progressively worsened over the previous decade. In addition, an unintentional 30-pound weight loss had occurred over several years. Six years previously, a diagnosis of hypersensitivity pneumonitis was made following right upper lobe wedge resection that revealed chronic bronchiolitis with interstitial pneumonia and non-necrotizing granulomatous inflammation. Subsequent use of prednisone elicited mild intermittent improvement. She had used feather pillows in the past without any other significant exposures. There were no reports of sinus or GI symptoms.

WebPalestra: cirurgia bariátrica no pós operatório tardio, sinais de alerta

Serão abordados os aspectos normais no pós operatório tardio (após 18 meses) e os sinais de alerta para investigação e referência ao cirurgião bariátrico.

Late-onset MADD: a rare cause of cirrhosis and acute liver failure?

Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a severe inborn error of fat metabolism. In late-onset MADD, hepatopathy in the form of steatosis is commonplace and considered a benign and stable condition that does not progress to more advanced stages of liver disease, however, progression to cirrhosis and acute liver failure (ALF) has been reported in two previous case reports. Here, we report a 22-year-old man, who suffered from late-onset MADD and died from cirrhosis and ALF. In the span of three months repeated clinical examinations, blood tests, and diagnostic imaging as well as liver biopsy revealed rapid progression of hepatopathy from steatosis to decompensated cirrhosis with portal hypertension. Routine studies for recognized etiologies found no evident cause besides MADD. This case report supports the findings of the two previous case reports and adds further evidence to the suggestion that late-onset MADD should be considered a rare cause of cirrhosis and ALF.

Working adeptly to diagnose and treat adult ADHD.

Rely on DSM-5 criteria and an appropriate rating scale to assess how an individual's inattention, hyperactivity, and impulsivity interfere with functioning in different settings.

Paranoid delusions • ideas of reference • sleep problems • Dx?

► Paranoid delusions ► Ideas of reference ► Sleep problems ► Multiple, vague somatic symptoms.

Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report.

BACKGROUND: The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion syndrome 7 and Perrault syndrome 5. Perrault syndrome is characterized by sensorineural hearing loss in both males and females and gonadal dysfunction in females. Patients with Perrault syndrome may present early-onset cerebellar ataxia, whereas middle-age-onset cerebellar ataxia caused by TWNK variants is rare. CASE PRESENTATION: A Japanese female born to consanguineous parents presented hearing loss at age 48, a staggering gait at age 53, and numbness in her distal extremities at age 57. Neurological examination revealed sensorineural hearing loss, cerebellar ataxia, decreased deep tendon reflexes, and sensory disturbance in the distal extremities. Laboratory tests showed no abnormal findings other than a moderate elevation of pyruvate concentration levels. Brain magnetic resonance imaging revealed mild cerebellar atrophy. Using exome sequencing, we identified a homozygous TWNK variant (NM_021830: c.1358G>A, p.R453Q). CONCLUSIONS: TWNK variants could cause middle-age-onset cerebellar ataxia. Screening for TWNK variants should be considered in cases of cerebellar ataxia associated with deafness and/or peripheral neuropathy, even if the onset is not early.

Clinical course and pathological findings of two late-onset Fabry hemizygous patients including mulberry cell counts after enzyme replacement therapy.

Fabry disease is an X-linked inherited lysosomal storage disorder caused by a deficiency of α-galactosidase A activity, resulting in the intracellular accumulation of globotriaosylceramide and related glycosphingolipids. The phenotypes of Fabry disease in both males and females are grouped into two categories: the classical type and the late-onset type. The classical type shows general symptoms including angiokeratoma(s), acroparesthesia, hypohidrosis, corneal opacity, and gastrointestinal symptoms from an early age. The late-onset type shows cardiac or renal (or both) symptoms from a late age. We present herein the clinical course and pathological findings of two late-onset hemizygous Fabry patients after the initiation of enzyme replacement therapy (ERT), along with their mulberry cell counts during treatment. One patient's case was a renal-variant type without general symptoms; he showed stable renal function and mild proteinuria but little histological improvement with no change in the mulberry cell count during ERT. The other patient had a cardiac-variant type with renal pathological abnormality. He achieved a mild improvement of renal pathological findings, and his mulberry cell count gradually decreased during the treatment. These findings indicate that monitoring the mulberry cell count might help assess the efficacy of ERT, as a renal pathology tool.

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study.

BACKGROUND: Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC. METHODS: In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter-related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry. RESULTS: In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter-related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11). CONCLUSIONS: Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.

The Value of Neuropsychological Assessment in the Differentiation Between Behavioral Variant Frontotemporal Dementia and Late-Onset Psychiatric Disorders.

OBJECTIVE: To investigate which neuropsychological tests can discriminate between behavioral variant frontotemporal dementia (bvFTD) and psychiatric disorders presenting with similar late-onset frontal behavioral changes, such as apathy, disinhibition, reduced empathy, or compulsive behavior. METHODS: Patients presenting with frontal behavioral changes in middle or late adulthood received extensive baseline examinations, including neuropsychological assessment and brain imaging. After 2 years, examinations were repeated and patients were diagnosed according to DSM-IV or international bvFTD consensus criteria. The study period was April 2011-June 2015. Two groups were selected: 32 patients with bvFTD and 53 patients with a psychiatric or psychological diagnosis. Associations between neuropsychological test scores and diagnostic group were investigated with logistic regression analyses, and diagnostic accuracy was investigated with a receiver operating characteristic curve. RESULTS: BvFTD patients scored lower on tests for confrontational naming, gestalt completion, and verbal abstraction compared to psychiatric patients (P < .01). The confrontational naming test (Boston Naming Test) showed the strongest association with diagnostic group: a lower score indicated a higher probability for a bvFTD diagnosis (P < .001). This test could discriminate between the groups with good diagnostic accuracy (area under the curve = 0.81). Tests for attention, memory, and executive functions showed no discriminative ability between the groups. CONCLUSIONS: Although one of the criteria of bvFTD is low performance on executive tests, these tests are not useful in differentiating bvFTD from psychiatric disorders. We recommend administering language tests, especially an extensive confrontational naming test, to aid differentiation between bvFTD and a psychiatric disorder in patients presenting with late-onset frontal behavioral changes.

Are changes in ADHD course reflected in differences in IQ and executive functioning from childhood to young adulthood?

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with poorer cognitive functioning. We used a developmental, genetically-sensitive approach to examine intelligence quotient (IQ) from early childhood to young adulthood among those with different ADHD courses to investigate whether changes in ADHD were reflected in differences in IQ. We also examined executive functioning in childhood and young adulthood among different ADHD courses. METHODS: Study participants were part of the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2232 twins. We assessed ADHD in childhood (ages 5, 7, 10 and 12) and young adulthood (age 18). We examined ADHD course as reflected by remission, persistence and late-onset. IQ was evaluated at ages 5, 12 and 18, and executive functioning at ages 5 and 18. RESULTS: ADHD groups showed deficits in IQ across development compared to controls; those with persistent ADHD showed the greatest deficit, followed by remitted and late-onset. ADHD groups did not differ from controls in developmental trajectory of IQ, suggesting changes in ADHD were not reflected in IQ. All ADHD groups performed more poorly on executive functioning tasks at ages 5 and 18; persisters and remitters differed only on an inhibitory control task at age 18. CONCLUSIONS: Differences in ADHD course - persistence, remission and late-onset - were not directly reflected in changes in IQ. Instead, having ADHD at any point across development was associated with lower average IQ and poorer executive functioning. Our finding that individuals with persistent ADHD have poorer response inhibition than those who remitted requires replication.

Late onset left ventricular dysfunction and cardiomyopathy induced with ibrutinib.

INTRODUCTION: Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase, has altered the treatment perspective of chronic lymphocytic leukemia and showed modest activity against several types of non-Hodgkin's lymphomas. According to phase studies and real-world data, reported serious adverse effects included atrial fibrillation, diarrhea, and bleeding diathesis. However, heart failure was not reported to be a probable adverse effect linked with ibrutinib. CASE REPORT: In this paper, we present a 66-year-old female chronic lymphocytic leukemia patient who developed significant and symptomatic left ventricular dysfunction at the 13th month of ibrutinib treatment. MANAGEMENT AND OUTCOME: Following cessation of ibrutinib, ejection fraction and clinical findings of the left ventricular dysfunction alleviated. DISCUSSION: Although the use of ibrutinib is generally well tolerated, cardiac functions should be monitored occasionally in all patients.

Late-onset unexplained epilepsy: What are we missing?

With the aging of the US population, the incidence of epilepsy will increase, with 25 to 50% of new cases with no identifiable etiology diagnosed as late-onset unexplained epilepsy (LOUE). In the current targeted review, we discuss the possible role of cerebral small vessel ischemic disease, accumulation of amyloidß and hyperphosphorylated tau, and sleep apnea as potential pathophysiologic mechanisms explaining LOUE. We highlight the impact of these processes on cognition and avenues for diagnosis and treatment.

Interventions to improve adherence to surveillance guidelines in survivors of childhood cancer: a systematic review.

PURPOSE: Many survivors of childhood cancer are at high risk of late effects of their cancer therapy, including cardiac toxicity and subsequent malignant neoplasms (SMN). Current North American guidelines recommend periodic surveillance for these late effects. We conducted a systematic review of the literature to estimate rates of adherence to recommended surveillance and summarize studies evaluating interventions intended to increase adherence. METHODS: We searched MEDLINE, Embase, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) for articles published between January 2000 and September 2018 that reported adherence to surveillance for cardiac toxicity and SMN (breast and colorectal cancer) and interventions implemented to improve completion of recommended testing. Risk of bias was assessed using relevant Cochrane checklists. Due to heterogeneity and overlapping study populations, we used narrative synthesis to summarize the findings. This review was registered in PROSPERO: CRD42018098878. RESULTS: Thirteen studies met our inclusion criteria for assessing adherence to surveillance, while five assessed interventions to improve rates of surveillance. No studies met criteria for low risk of bias. Completion of recommended surveillance was lowest for colorectal cancer screening (11.5-30.0%) followed by cardiomyopathy (22.3-48.1%) and breast cancer (37.0-56.5%). Factors such as patient-provider communication, engagement with the health care system, and receipt of information were consistently reported to be associated with higher rates of surveillance. Of five randomized controlled trials aimed at improving surveillance, only two significantly increase completion of recommended testing-one for echocardiography and one for mammography. Both involved telephone outreach to encourage and facilitate these tests. CONCLUSION: The majority of childhood cancer survivors at high risk of cardiac toxicity or SMN do not receive evidence-based surveillance. There is paucity of rigorous studies evaluating interventions to increase surveillance in this population. IMPLICATIONS FOR CANCER SURVIVORS: Robust trials are needed to assess whether tailored interventions, designed based on unique characteristics and needs of each survivor population, could improve adherence.