Pyridostigmine induced heart block requiring ICU admission.

Myasthenia gravis is an autoimmune disorder that effects an estimated 20 people per 100,000 in the USA per year. Pyridostigmine is a common drug used in the symptomatic treatment of myasthenia gravis. While generally safe and effective, a rare set of patients treated with pyridostigmine encounter cardiac conduction disorders. Here, we report a rare presentation of an adverse drug reaction due to pyridostigmine, which is important for its implications in the acute care setting.

Longitudinal assessment of falls in patients with Parkinson's disease using inertial sensors and the Timed Up and Go test.

OBJECTIVE: To examine the predictive validity of a TUG test for falls risk, quantified using body-worn sensors (QTUG) in people with Parkinson's Disease (PD). We also sought to examine the inter-session reliability of QTUG sensor measures and their association with the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. APPROACH: A six-month longitudinal study of 15 patients with Parkinson's disease. Participants were asked to complete a weekly diary recording any falls activity for six months following baseline assessment. Participants were assessed monthly, using a Timed Up and Go test, quantified using body-worn sensors, placed on each leg below the knee. MAIN RESULTS: The results suggest that the QTUG falls risk estimate recorded at baseline is 73.33% (44.90, 92.21) accurate in predicting falls within 90 days, while the Timed Up and Go time at baseline was 46.67% (21.27, 73.41) accurate. The Timed Up and Go time and QTUG falls risk estimate were strongly correlated with UPDRS motor score. Fifty-two of 59 inertial sensor parameters exhibited excellent inter-session reliability, five exhibited moderate reliability, while two parameters exhibited poor reliability. SIGNIFICANCE: The results suggest that QTUG is a reliable tool for the assessment of gait and mobility in Parkinson's disease and, furthermore, that it may have utility in predicting falls in patients with Parkinson's disease.

Asymmetric responsiveness of disability and health-related quality of life to improvement versus decline in Parkinson's disease.

PURPOSE: Clinical trials in Parkinson's disease commonly employ outcome measures of disability and quality of life. Responsiveness of these outcomes measures to symptomatic decline versus improvement has not been studied. We wanted to study the responsiveness of Schwab & England Activities of Daily Living Scale (SE) and Short Form-12 (SF-12) to symptomatic decline versus improvement in Parkinson's disease over a 4-year period among a naturalistic cohort of patients. METHODS: Parkinson's disease patients (N = 228, disease duration 6.1 years) were followed for 4 years with assessments of disease severity, Unified Parkinson's Disease Rating Scale (UPDRS), health-related quality of life (SF-12 physical/mental health), and disability (SE). The sample was subdivided into those who declined (N = 118) or improved (N = 102) on total-UPDRS. Responsiveness was assessed with Cohen's effect size and standardized response mean. RESULTS: At baseline, patients who improved over 4 years had greater disease severity and worse quality of life than decliners (p < .05). Decliners had a 13.5-point worsening on total-UPDRS, 26.3-39.8; p < .001) associated with concomitant decline on the SF-12 (physical health 42.9-39.2, mental health 50.0-46.6; both p < .001) and the SE (85-74 %; p < .001). Improvers had a 13.0-point improvement on total-UPDRS (39.8-26.8; p < .001) associated with minimal change on the SF-12 (physical health 40.8-39.5, mental health 47.1-46.3) and SE (79-79 %). Based on effect size, the rank order of responsiveness of measures for decliners from high to low was SE (-0.78), Short Form-12 mental health (-0.45), and SF-12 physical health (-0.34). Rank order of responsiveness for improvers was Short Form-12 physical health (-0.11), SF-12 mental health (-0.10), and SE (-0.03). CONCLUSIONS: Among decliners, measures of disability and quality of life were moderate to highly responsive to change in disease severity. Among improvers, both disability and quality of life were poorly responsive despite UPDRS improvement of comparable magnitude.

Possible Functional Moving Toes Syndrome.

BACKGROUND: Moving toes syndrome has been classically described as an organic movement disorder, on occasion related to peripheral nerve injuries. The association between nerve trauma and movement disorders has become a controversial topic, and the functional etiology of moving toes syndrome has recently been proposed. CASE REPORT: We describe two cases of moving toes syndrome with clinical features typically suggestive of a functional movement disorder. DISCUSSION: The presence of entrainability and distractibility in the described patients is an indication of attentional influences on their involuntary movements. However, it is possible that if there is a subcortical origin, the toe movements could be influenced by voluntary commands.

Update on secondary prevention of ischaemic stroke.

Stroke is becoming a major cause of morbidity and mortality in the developing world while the trend is actually downward in the developed nations. This is mostly because of the better recognition, treatment options and secondary prevention in addition to changes in lifestyles. There have been significant developments in the secondary prevention of ischaemic stroke in the last decade alone. Newer medications like direct thrombin inhibitors and factor Xa inhibitors have come into common practice. These medications are either equally effective or even better than age-old warfarin. Unlike previous belief, we now know that mechanical closure of the patent foramen ovale does not reduce the rate of stroke recurrence. There is a hint that dual anti-platelet therapy may reduce early recurrence of stroke. Even more exciting news is that closure of left atrial appendage might totally eliminate the need for oral anticoagulation in selected patient population.

Treating epilepsy in the setting of medical comorbidities.

OPINION STATEMENT: Treatment of epilepsy in patients with medical comorbidities can be challenging. Comorbidities can affect medical management and quality of life. In this review, we discuss treatment options in patients with epilepsy and medical comorbidities. In our opinion, the best way to manage patients with medical comorbidities and epilepsy is to accurately recognize and diagnose medical comorbidities, and to have adequate knowledge and familiarity with antiepileptic drug (AED) metabolism, dosing, side effects, and drug interactions. We believe the trend should move toward using the newer generation of AEDs given their generally reduced rate of adverse effects and interactions. The primary goal of therapy is seizure freedom without side effects.

Executive dysfunction in Parkinson's disease and timing deficits.

Patients with Parkinson's disease (PD) have deficits in perceptual timing, or the perception and estimation of time. PD patients can also have cognitive symptoms, including deficits in executive functions such as working memory, planning, and visuospatial attention. Here, we discuss how PD-related cognitive symptoms contribute to timing deficits. Timing is influenced by signaling of the neurotransmitter dopamine in the striatum. Timing also involves the frontal cortex, which is dysfunctional in PD. Frontal cortex impairments in PD may influence memory subsystems as well as decision processes during timing tasks. These data suggest that timing may be a type of executive function. As such, timing can be used to study the neural circuitry of cognitive symptoms of PD as they can be studied in animal models. Performance of timing tasks also maybe a useful clinical biomarker of frontal as well as striatal dysfunction in PD.

New AP4B1 mutation in an African-American child associated with intellectual disability.

Prevalence of intellectual disability (ID) varies from 1-3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously.