Impact of the metabolic syndrome on prevalence and survival in motor neuron disease: a retrospective case series.

Metabolic dysfunction is an important factor in the pathogenesis of motor neuron disease, but its prevalence and association with survival in this disorder is unknown. We hypothesized that patients with motor neuron disease would show a higher prevalence of metabolic syndrome compared to the general New Zealand population, and that metabolic syndrome would be associated with worsened survival. We undertook a retrospective analysis in 109 motor neuron disease patients diagnosed and treated at Waikato Hospital from 2013 to 2020. Demographic, clinical, and laboratory data were collected. Survival was defined as the date of initial symptom onset to the date of death. Of 104 eligible patients, 34 patients (33%) had metabolic syndrome (33% of Europeans, 46% of Maori). Mean survival in motor neuron disease patients with metabolic syndrome was significantly reduced compared to patients without metabolic syndrome (38 vs. 61 months, P = 0.044), with a 5-year survival rate of 21% for the former and 38% for the latter (P = 0.012). Compared with the general New Zealand population, metabolic syndrome is highly prevalent amongst motor neuron disease patients in the Waikato region and it is associated with worsened survival. Metabolic dysfunction may be a key factor underlying the pathogenesis of motor neuron disease.

Aminophylline in pain and migraine.

Although the pathogenesis of migraine is not fully understood, accumulating evidence indicates migraine may be driven by impaired brain energy metabolism in the context of pathologically high levels of adenosine. Considerable evidence indicates that aminophylline, an adenosine receptor antagonist, can provide strong therapeutic relief in pain, particularly post-dural headache. Moreover, direct observations from a previously published observational case series have demonstrated a strong therapeutic impact of low-dose aminophylline in patients with severe, unremitting migraine attacks. Although higher doses of aminophylline are associated with an unfavourable adverse effect profile, low doses of aminophylline are associated with minimal adverse effects. Despite this promise, double-blinded randomized trials will be needed to determine the true therapeutic efficacy of low-dose aminophylline in migraine.

Metabolic Strategies in Healthcare: A New Era.

Modern healthcare systems are founded on a disease-centric paradigm, which has conferred many notable successes against infectious disorders in the past. However, today's leading causes of death are dominated by non-infectious "lifestyle" disorders, broadly represented by the metabolic syndrome, atherosclerosis, cancer, and neurodegeneration. Our disease-centric paradigm regards these disorders as distinct disease processes, caused and driven by disease targets that must be suppressed or eliminated to clear the disease. By contrast, a health-centric paradigm recognizes the lifestyle disorders as a series of hormonal and metabolic responses to a singular, lifestyle-induced disease of mitochondria dysfunction, a disease target that must be restored to improve health, which may be defined as optimized mitochondria function. Seen from a health-centric perspective, most drugs target a response rather than the disease, whereas metabolic strategies, such as fasting and carbohydrate-restricted diets, aim to restore mitochondria function, mitigating the impetus that underlies and drives the lifestyle disorders. Substantial human evidence indicates either strategy can effectively mitigate the metabolic syndrome. Preliminary evidence also indicates potential benefits in atherosclerosis, cancer, and neurodegeneration. Given the existing evidence, integrating metabolic strategies into modern healthcare systems should be identified as a global health priority.

Perry syndrome: a case of atypical parkinsonism with confirmed DCTN1 mutation.

Perry syndrome is a rare neurological condition characterised clinically by depression, sleep disturbance, central hypoventilation and parkinsonism. Perry syndrome is a TAR DNA-binding protein 43 (TDP-43) proteinopathy associated with mutated dynactin-1 protein, inherited in an autosomal dominant manner. Several pathogenic mutations in exon 2 in the dynactin 1 gene have been identified; p. F521, p. G67d, p. G71R, p. G71E, p. G71A, p. T72p, p. Q74p and p. Y78C. We present the second known case Perry syndrome with confirmed DCTN1 mutation (p. Y78C) in New Zealand, who initially was thought to have a depressive illness. Perry syndrome should be considered in the differential diagnosis of young parkinsonism, especially if there is family history of sleep disorders, weight loss and/or marked depression.