Urinary oligosaccharides in lysosomal and other metabolic disorders

This review describes the methods and results obtained in the study of the urinary oligosaccharides in some metabolic disorders, lysosomal and other metabolic disorders. Attention is focused especially on thin layer chromatography, which, being so simple, may be regarded as a useful method of screening for these diseases.

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Sommario Vengono descritti i metodi ed i risultati ottenuti nello studio degli oligosaccaridi urinari in alcune malattie dismetaboliche di natura lisosomiale e non. Viene focalizzata l'attenzione in modo particolare sulla cromatografia su strato sottile che, essendo una metodica semplice ed economica, può essere considerata un utile mezzo di screening per tali disturbi.

     

Previously unknown thyroid dysfunction in patients with acute ischemic stroke

Bengtsson D, Brudin L, Wanby P, Carlsson M. Previously unknown thyroid dysfunction in patients with acute ischemic stroke.
Acta Neurol Scand: 2012: 126: 98–102
© 2011 John Wiley & Sons A/S. Objectives – Opinions differ regarding the clinical significance of subclinical thyroid disorders. The aim of the present study was to evaluate the prevalence and influence of previously unknown overt or subclinical thyroid dysfunction in patients with acute ischemic stroke and to look for differences between cardio‐embolic and non‐embolic ischemic stroke. Material and methods – A total of 153 Swedish patients diagnosed with first‐time acute ischemic stroke were included in the study and categorized for suspected cardio‐embolic (n = 30) or non‐embolic (n = 123) ischemic stroke depending on the presence of atrial fibrillation (AF). Blood samples were taken 48 h or earlier after onset of stroke symptoms. Results – Previously, unknown overt or subclinical thyroid dysfunction was found in 12%. Previously, unknown overt or subclinical hyperthyroidism was more common in the AF group (13%) compared to the non‐AF group (3%), P = 0.048. Patients with AF had slightly higher concentrations of free T4 (15 vs 14 pm ; P < 0.001), but there was no significant difference in concentrations of S‐TSH or prevalence of thyroperoxidase (TPO) antibodies between the groups. Conclusions – In patients with first‐time acute ischemic stroke, unknown thyroid dysfunction is common, and unknown overt or subclinical hyperthyroidism is associated with cardio‐embolic stroke.     

Hashimoto encephalopathy: literature review

Hashimoto encephalopathy (HE) presents as an encephalopathy without central nervous system infection or tumor. HE is associated with autoimmune thyroiditis and is thus considered to be an autoimmune disorder. The prevalence of HE is low, but death and status epilepticus have been reported. HE manifests with a wide range of symptoms that include behavioral changes and confusion. Elevated thyroid antibodies are present in the majority of cases and are required for the diagnosis of HE. Normal brain MRI findings are found in the majority of patients diagnosed with HE. The most consistent CSF abnormality noted in HE patients is the presence of elevated protein. Most HE patients respond well to steroid therapy. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis. In conclusion, it is now generally accepted that the diagnosis of HE must include encephalopathy characterized by cognitive impairment associated with psychiatric features, such as hallucinations, delusions, and paranoia. Autoimmune encephalitis and prion disease should be considered in the differential diagnosis due to the similarity of the clinical features of these conditions to those of HE.     

The METEOR study of diabetes and other metabolic disorders in patients with schizophrenia treated with antipsychotic drugs. I. Methodology

Patients with schizophrenia present a two‐ to three‐fold higher prevalence of diabetes, of metabolic syndrome and of cardiovascular morbidity. The reason for this increased prevalence may involve intrinsic vulnerability, lifestyle factors and iatrogenic effects of antipsychotic drugs. The objective of this multinational, cross‐sectional, pharmacoepidemiological study was to determine the prevalence of diabetes, lipid disorders, obesity, hypertension and the metabolic syndrome in patients with schizophrenia treated with antipsychotic drugs. Particular attention was taken to acquire data on a wide a range as possible of demographic, clinical and lifestyle variables that may influence the risk of metabolic disorders, which were taken into account in the calculation of prevalence data by propensity scoring. The study included 2270 subjects from 16 European countries, predominantly from Central and Eastern Europe. The proportion of subjects presenting the pathologies of interest was relatively high, ranging from 28% for glycaemic disorders to 70% for lipid disorders. Copyright © 2010 John Wiley & Sons, Ltd.     

Rhabdomyolysis: a review

Rhabdomyolysis, a syndrome of skeletal muscle breakdown with leakage of muscle contents, is frequently accompanied by myoglobinuria, and if sufficiently severe, acute renal failure with potentially life-threatening metabolic derangements may ensue. A diverse spectrum of inherited and acquired disorders affecting muscle membranes, membrane ion channels, and muscle energy supply causes rhabdomyolysis. Common final pathophysiological mechanisms among these causes of rhabdomyolysis include an uncontrolled rise in free intracellular calcium and activation of calcium-dependent proteases, which lead to destruction of myofibrils and lysosomal digestion of muscle fiber contents. Recent advances in molecular genetics and muscle enzyme histochemistry may enable a specific metabolic diagnosis in many patients with idiopathic recurrent rhabdomyolysis.     

Atypical Wernicke's encephalopathy showing lesions in the cranial nerve nuclei and cerebellum.

Wernicke's encephalopathy (WE) is a severe neurological disorder caused by a dietary deficiency of Vitamin B1 and characterized by consciousness changes, ocular abnormalities, and ataxia. Wernicke's encephalopathy is considered a medical emergency and treatment consists of intravenous thiamine administration. Typically in alcoholic and nonalcoholic patients magnetic resonance shows alterations in the mamillary bodies, medial thalami, tectal plate, and periaqueductal regions. We report here on a nonalcoholic atypical case of WE which presented with reversible symmetrical lesions in the cranial nerves nuclei and in the cerebellum alongside the classic neuroradiological findings.     

Neurological outcome in 22 treated adolescents with hyperphenylalaninemia

We examined clinically and electrophysiologically 22 adolescents suffering from hyperphenylalaninemia. Three of 16 treated patients showed slight impairment of proprioception; their examination was otherwise unremarkable. Subclinical deficits were present in the central motor and sensory pathway. In addition, we had evidence of a minor sensory neuropathy: 32% of the 22 patients had subclinical deficits in the visual system. However, in contrast to earlier reports we saw no relation to the degree of metabolic control. Our results suggest that treated adolescent patients with hyperphenylalaninemia show neurological dysfunction that may be related to morphological, as well as pharmacological changes.     

Movement disorders in adult surviving patients with maple syrup urine disease

Maple syrup urine disease is a rare metabolic disorder caused by mutations in the branched‐chain α‐keto acid dehydrogenase complex gene. Patients generally present early in life with a toxic encephalopathy because of the accumulation of the branched‐chain amino acids leucine, isoleucine, and valine and the corresponding ketoacids. Movement disorders in maple syrup urine disease have typically been described during decompensation episodes or at presentation in the context of a toxic encephalopathy, with complete resolution after appropriate dietary treatment. Movement disorders in patients surviving childhood are not well documented. We assessed 17 adult patients with maple syrup urine disease (mean age, 27.5 years) with a special focus on movement disorders. Twelve (70.6%) had a movement disorder on clinical examination, mainly tremor and dystonia or a combination of both. Parkinsonism and simple motor tics were also observed. Pyramidal signs were present in 11 patients (64.7%), and a spastic‐dystonic gait was observed in 6 patients (35.2%). In summary, movement disorders are common in treated adult patients with maple syrup urine disease, and careful neurological examination is advisable to identify those who may benefit from specific therapy. © 2011 Movement Disorder Society     

Metabolic epilepsy: An update

Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. Presentation is usually in the neonatal period or infancy but can occur at any time, even in adulthood. Seizures are frequent symptom in inborn errors of metabolism, with no specific seizure types or EEG signatures. The diagnosis of a genetic defect or an inborn error of metabolism often results in requests for a vast array of biochemical and molecular tests leading to an expensive workup. However a specific diagnosis of metabolic disorders in epileptic patients may provide the possibility of specific treatments that can improve seizures. In a few metabolic diseases, epilepsy responds to specific treatments based on diet or supplementation of cofactors (vitamin-responsive epilepsies), but for most of them specific treatment is unfortunately not available, and conventional antiepileptic drugs must be used, often with no satisfactory success. In this review we present an overview of metabolic epilepsies based on various criteria such as treatability, age of onset, seizure type, and pathogenetic background.     

Burden of general medical conditions among individuals with bipolar disorder

OBJECTIVE: Treatment of coexisting medical comorbidities may reduce the risk of adverse outcomes among patients with bipolar disorder. We determined the prevalence of general medical conditions in a population-based sample of patients diagnosed with bipolar disorder in the Veterans Administration (VA). METHODS: We conducted a cross-sectional study of patients (n = 4310) diagnosed with bipolar disorder in fiscal year 2001 receiving care at VA facilities located within the mid-Atlantic region. General medical conditions were assessed using ICD-9 codes, and we compared the prevalence of each condition in our bipolar sample with national data on the VA patient population. RESULTS: The mean age was 53 (SD = 13), 10% were women, and 12% African-American. The mean age of the VA national patient population was higher (58 years). The most prevalent conditions among patients with bipolar disorder included cardiovascular (e.g. hypertension, 35%), endocrine (e.g. hyperlipidemia, 23%; diabetes, 17%), and alcohol use disorder (25%). When compared with national data, the prevalence of diabetes was higher in the bipolar cohort than in the national cohort (17.2% versus 15.6%; p = 0.0035). Hepatitis C was more common in the bipolar group than the national cohort (5.9% versus 1.1%; p < 0.001). Lower back pain (15.4% versus 10.6%; p < 0.0001) and pulmonary conditions (e.g. COPD: 10.6% versus 9.4%; p = 0.005) were also more prevalent among the bipolar cohort than the VA national cohort. CONCLUSIONS: Individuals with bipolar disorder possess a substantial burden of general medical comorbidity, and are occurring at an earlier age than in the general VA patient population, suggesting the need for earlier detection and treatment for patients with bipolar disorder.     

线粒体病血液氨基酸谱和酰基肉碱谱的改变特点

目的研究线粒体病患者血液氨基酸谱和酰基肉碱谱的变化特点。方法对50例线粒体病、20例多酰基辅酶A脱氢酶缺陷(MADD)患者和22名健康对照,使用串联质谱法检测血液中氨基酸和酰基肉碱水平。选取线粒体病组与MADD组、健康对照组分别比较差异均有统计学意义(均P0.05),而MADD组同健康对照组比较差异无统计学意义(P≥0.05)的氨基酸、酰基肉碱相关指标绘制ROC曲线,选取曲线下面积(AUC)最大的指标,计算其诊断线粒体病的敏感度、特异度。结果线粒体病组谷氨酸及鸟氨酸水平分别为中位数89.80μmol/L、27.70μmol/L,均低于MADD组(中位数113.46μmol/L、33.52μmol/L,均P0.05)和健康对照组(中位数107.33μmol/L、34.08μmol/L,均P0.001),丙氨酸/谷氨酸比值(中位数2.72)高于MADD组(中位数1.86,P0.05)和健康对照组(中位数1.55,P0.001)。线粒体病组乙酰肉碱、羟丁酰肉碱、羟异戊酰肉碱、戊二酰肉碱、羟棕榈酰肉碱水平分别为中位数27.25μmol/L、0.28μmol/L、0.33μmol/L、0.10μmol/L、0.08μmol/L,均高于MADD组(中位数21.32μmol/L、0.17μmol/L、0.19μmol/L、0.09μmol/L、0.06μmol/L,均P0.05)和健康对照组(中位数21.26μmol/L、0.18μmol/L、0.20μmol/L、0.07μmol/L、0.05μmol/L,均P0.01)。对上述氨基酸、酰基肉碱指标绘制ROC曲线,其中丙氨酸/谷氨酸比值AUC 0.864,当丙氨酸/谷氨酸比值2.17时诊断线粒体病的敏感度和特异度分别为76.00%和85.71%。结论线粒体病的血氨基酸和酰基肉碱改变具有一定规律,有可能作为该类疾病的辅助检查方法。     

Valproate-induced hyperammonemic encephalopathy

Valproate-induced hyperammonemic encephalopathy (VHE) is an unusual complication characterized by a decreasing level of consciousness, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy. We have thoroughly reviewed the predisposing factors and their screening, the biochemical and physiopathological mechanisms involved, the different treatments described, and those that are being investigated. Etiopathogenesis is not completely understood, although hyperammonemia has been postulated as the main cause of the clinical syndrome. The increase in serum ammonium level is due to several mechanisms, the most important one appearing to be the inhibition of carbamoylphosphate synthetase-I, the enzyme that begins the urea cycle. Polytherapy with several drugs, such as phenobarbital and topiramate, seems to contribute to hyperammonemia. Hyperammonemia leads to an increase in the glutamine level in the brain, which produces astrocyte swelling and cerebral edema. There are several studies that suggest that treatment with supplements of carnitine can lead to an early favorable clinical response due to the probable carnitine deficiency induced by a valproate (VPA) treatment. Development of the progressive confusional syndrome, associated with an increase in seizure frequency after VPA treatment onset, obliges us to rule out VHE by screening for blood ammonium levels and the existence of urea cycle enzyme deficiency, such as ornithine carbamoyltransferase deficiency. Electroencephalography (EEG) is characterized by signs of severe encephalopathy with continuous generalized slowing, a predominance of theta and delta activity, occasional bursts of frontal intermittent rhythmic delta activity, and triphasic waves. These EEG findings, as well as clinical manifestations and hyperammonemia, tend to normalize after VPA withdrawal.     

Brain PET substrate of impulse control disorders in Parkinson's disease: A metabolic connectivity study

Impulse control disorders (ICDs) have received increased attention in Parkinson's disease (PD) because of potentially dramatic consequences. Their physiopathology, however, remains incompletely understood. An overstimulation of the mesocorticolimbic system has been reported, while a larger network has recently been suggested. The aim of this study is to specifically describe the metabolic PET substrate and related connectivity changes in PD patients with ICDs. Eighteen PD patients with ICDs and 18 PD patients without ICDs were evaluated using cerebral 18F‐fluorodeoxyglucose positron emission tomography. SPM‐T maps comparisons were performed between groups and metabolic connectivity was evaluated by interregional correlation analysis (IRCA; p < .005, uncorrected; k > 130) and by graph theory (p < .05). PD patients with ICDs had relative increased metabolism in the right middle and inferior temporal gyri compared to those without ICDs. The connectivity of this area was increased mostly with the mesocorticolimbic system, positively with the orbitofrontal region, and negatively with both the right parahippocampus and the left caudate (IRCA). Moreover, the betweenness centrality of this area with the mesocorticolimbic system was lost in patients with ICDs (graph analysis). ICDs are associated in PD with the dysfunction of a network exceeding the mesocorticolimbic system, and especially the caudate, the parahippocampus, and the orbitofrontal cortex, remotely including the right middle and inferior temporal gyri. This latest area loses its central place with the mesocorticolimbic system through a connectivity dysregulation.