Lamotrigine Therapy and Biomarkers of Cerebral Energy Metabolism in Older Age Bipolar Depression.

OBJECTIVE: This study compared brain energy metabolism, as measured by cerebral concentrations of glutamate (Glu), glutamine (Gln), and N-acetyl aspartate (NAA), in older age bipolar depression (OABD) to that of psychiatrically healthy comparison subjects using proton (1H) magnetic resonance spectroscopy imaging at 4-Tesla. Metabolite levels were assessed in OABD subjects before and after 8 weeks of lamotrigine therapy with the goal of determining relationships between cerebral energy metabolism, depression symptom severity, and changes in depression symptom response. METHODS: Individuals (n = 21, mean age: 62.0 ± 5.9 years) with bipolar disorder, current episode depressed, and a healthy comparison group (n = 14, mean age: 67.5 ± 8.8 years) were selected. Participants with bipolar disorder, current episode depressed, were treated in open label fashion with lamotrigine monotherapy for 8 weeks. All subjects were scanned with 1H magnetic resonance spectroscopy at 4T at baseline and again after 8 weeks to assess levels of cerebral metabolites in the anterior cingulate cortex and parieto-occipital cortex. Metabolite levels were examined as ratios relative to creatine (Cr). Response to 8 weeks of lamotrigine treatment in the bipolar disorder, current episode depressed group, was assessed as a continuous measure on the Montgomery-Asberg Depression Rating Scale. RESULTS: NAA/Cr ratio in OABD was significantly lower by 14% (95% confidence interval: [1%, 26%]) than in comparison subjects at baseline. However, there were no associations between NAA/Cr, Glu/Cr, or Gln/Cr and either depression severity or lamotrigine treatment. CONCLUSION: Group differences in NAA suggest evidence for a deficit in cerebral energy metabolism in OABD.

Multiple sclerosis with megacystic presentation: A case report.

Multiple sclerosis is a frequent condition where the diagnosis relies on clinical presentation, neurologic examination, cerebro spinal fluid markers, and diagnostic imaging tests; however, atypical variants of the disease can lead to misdiagnosis in some scenarios. Herein, we describe a case of a 24-year-old patient with multiple sclerosis with megacystic plaques, in which appropriate interpretation of the imaging findings lead to a proper diagnosis and treatment.

Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver.

The deficiency of CITRIN, the liver mitochondrial aspartate-glutamate carrier (AGC), is the cause of four human clinical phenotypes, neonatal intrahepatic cholestasis caused by CITRIN deficiency (NICCD), silent period, failure to thrive and dyslipidemia caused by CITRIN deficiency (FTTDCD), and citrullinemia type II (CTLN2). Clinical symptoms can be traced back to disruption of the malate-aspartate shuttle due to the lack of citrin. A potential therapy for this condition is the expression of aralar, the AGC present in brain, to replace citrin. To explore this possibility we have first verified that the NADH/NAD+ ratio increases in hepatocytes from citrin(-/-) mice, and then found that exogenous aralar expression reversed the increase in NADH/NAD+ observed in these cells. Liver mitochondria from citrin (-/-) mice expressing liver specific transgenic aralar had a small (~ 4-6 nmoles x mg prot-1 x min-1) but consistent increase in malate aspartate shuttle (MAS) activity over that of citrin(-/-) mice. These results support the functional replacement between AGCs in the liver. To explore the significance of AGC replacement in human therapy we studied the relative levels of citrin and aralar in mouse and human liver through absolute quantification proteomics. We report that mouse liver has relatively high aralar levels (citrin/aralar molar ratio of 7.8), whereas human liver is virtually devoid of aralar (CITRIN/ARALAR ratio of 397). This large difference in endogenous aralar levels partly explains the high residual MAS activity in liver of citrin(-/-) mice and why they fail to recapitulate the human disease, but supports the benefit of increasing aralar expression to improve the redox balance capacity of human liver, as an effective therapy for CITRIN deficiency.

A rare cause of adult's epileptic crisis: Infratentorial multinodular and vacuolating neuronal tumor.

Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a rare and benign lesion which has been recently included in World Health Organization Classification of the central nervous system tumors. Another entity of lesions would present the same radiological characteristics; however, it would be in the posterior fossa, hence its name: infratentorial multinodular and vacuolating neuronal tumor. They are frequently characterized by the presence of cystic (or cyst-like) nodular lesions and may show cortical involvement. They mainly can be differentiated from other cystic entities, by their clustered and unchanging nature over time. We present the case of a 54-year-old patient who has consulted for epileptic seizures. Magnetic Resonance Imaging showed a multicystic-looking mass involving the vermis and the left cerebellar hemisphere that had no changes at follow-up in the last year suggestive of infratentorial multinodular and vacuolating neuronal tumor.

Role of diagnostic imaging in Rasmussen's encephalitis - A case report from Nepal.

Rasmussen's encephalitis (RE) is a relatively rare chronic inflammatory neurological disease that usually only affects one hemisphere of the brain. It primarily affects children under the age of 10, although it can also affect teens and adults, causing drug-resistant seizures, progressive hemiparesis, and dementia. RE presents as a challenging diagnosis with MRI as the cornerstone of the evaluation and nuclear imaging as a complementary tool. We'd like to present a case of a 12-year-old girl who was diagnosed with RE after an MRI. In this study, we examine the diagnostic criteria, differential diagnoses, and issues that underpin the diagnostic challenge in great detail.

Role of MRI in X-linked adrenoleukodystrophy-A case report.

X-linked adrenoleukodystrophy is a rare inherited peroxisomal disorder that occurs due to a genetic mutation. This mutation impairs normal transport of very long-chain fatty acids (VLCFAs) into peroxisomes, hence impeding VLCFA breakdown leading to its accumulation in plasma and tissues of the body. Due to its X-linked inheritance, it classically affects young males with most cases diagnosed during childhood. There are characteristic MRI findings in brain which can aid in diagnosis of X-ALD. We hereby present a case of a 10-year-old boy who presented with neurological and behavioral deterioration with MRI findings suggestive of X-ALD. MRI not only aids in diagnosis of X-ALD but can also identify the pattern of brain involvement which serves an important role in prognosis and outcome of the disease.

White Matter Measures and Cognition in Schizophrenia.

White matter (WM) abnormalities are commonly reported in schizophrenia but whether these arise from the axon or myelin compartments or both is not known. In addition, the relationship between WM abnormalities and cognitive function is not fully explored in this condition. We recruited 39 individuals with schizophrenia spectrum disorders and 37 healthy comparison subjects. All participants underwent MRI scanning at 4 Tesla to collect data in the prefrontal white matter on magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) which provide information on myelin and axon compartments, respectively. We also collected Matrics Composite Cognitive Battery (MCCB) and Stroop cognitive data. We found an elevated N-acetylaspartate (NAA) apparent diffusion coefficient in schizophrenia in this cohort as in our previous work; we also observed poorer performance on both the MCCB composite and the Stroop in schizophrenia patients compared to controls. The MTR measure was correlated with the MCCB composite (r = 0.363, p = 0.032) and Stroop scores (r = 0.387, p = 0.029) in healthy individuals but not in schizophrenia. Since this is the first exploration of the relationship between these WM and cognitive measures, we consider our analyses exploratory and did not adjust for multiple comparisons; the findings are not statistically significant if adjusted for multiple comparisons. These findings indicate that WM integrity is associated with cognitive function in healthy individuals but this relationship breaks down in patients with schizophrenia.

United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts.

As part of the United States Pharmacopeia's ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 mg to ∼1000 mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)."

Lhermitte-Duclos disease: A case report with radiologic-pathologic correlation.

Background: Lhermitte-Duclos disease (LDD) stems from the development of a rare benign lesion of uncertain pathogenesis that distorts the normal cerebellar laminar cytoarchitecture. We explored the lesion's appearance on conventional magnetic resonance imaging (MRI) combined with susceptibility-weighted imaging, diffusion-weighted imaging, perfusion imaging, or arterial spin labeling. Although many cases of LDD have been previously reported in the literature, the radiologic-pathologic correlation has been described in only a few of these cases. To the best of our knowledge, this is the first case report to provide detailed information about the radiologic-pathologic correlation of LDD. Case Report: A 48-year-old woman presented with left facial tics, occipital headache, and dizziness for 1 month. MRI revealed a left cerebellar lesion with hypointensity on T1-weighted images. On T2-weighted images, the mass was hyperintense with tigroid appearance due to alternating high and normal signal intensities. High signal intensity was noted on fluid-attenuated inversion recovery images. Magnetic resonance spectroscopy indicated decreased level of choline (Cho), N-acetyl aspartate, and myoinositol with elevated level of lactate on the affected side. The lesion showed a bright signal on diffusion-weighted images, whereas apparent diffusion coefficient mapping revealed no disturbance of diffusion. The pathology of the excised lesion was consistent with LDD. Conclusion: MRI with advanced techniques can provide not only preoperative diagnosis but also better pathologic correlation.

AExaCTT - Aerobic Exercise and Consecutive Task-specific Training for the upper limb after stroke: Protocol for a randomised controlled pilot study.

Motor function may be enhanced if aerobic exercise is paired with motor training. One potential mechanism is that aerobic exercise increases levels of brain-derived neurotrophic factor (BDNF), which is important in neuroplasticity and involved in motor learning and motor memory consolidation. This study will examine the feasibility of a parallel-group assessor-blinded randomised controlled trial investigating whether task-specific training preceded by aerobic exercise improves upper limb function more than task-specific training alone, and determine the effect size of changes in primary outcome measures. People with upper limb motor dysfunction after stroke will be allocated to either task-specific training or aerobic exercise and consecutive task-specific training. Both groups will perform 60 hours of task-specific training over 10 weeks, comprised of 3 × 1 hour sessions per week with a therapist and 3 × 1 hours of home-based self-practice per week. The combined intervention group will also perform 30 minutes of aerobic exercise (70-85%HRmax) immediately prior to the 1 hour of task-specific training with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events will be recorded. Clinical outcome measures will be performed pre-randomisation at baseline, at completion of the training program, and at 1 and 6 months follow-up. Primary clinical outcome measures will be the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT). If aerobic exercise prior to task-specific training is acceptable, and a future phase 3 randomised controlled trial seems feasible, it should be pursued to determine the efficacy of this combined intervention for people after stroke.

Comparison of unsupervised classification methods for brain tumor segmentation using multi-parametric MRI.

Tumor segmentation is a particularly challenging task in high-grade gliomas (HGGs), as they are among the most heterogeneous tumors in oncology. An accurate delineation of the lesion and its main subcomponents contributes to optimal treatment planning, prognosis and follow-up. Conventional MRI (cMRI) is the imaging modality of choice for manual segmentation, and is also considered in the vast majority of automated segmentation studies. Advanced MRI modalities such as perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) have already shown their added value in tumor tissue characterization, hence there have been recent suggestions of combining different MRI modalities into a multi-parametric MRI (MP-MRI) approach for brain tumor segmentation. In this paper, we compare the performance of several unsupervised classification methods for HGG segmentation based on MP-MRI data including cMRI, DWI, MRSI and PWI. Two independent MP-MRI datasets with a different acquisition protocol were available from different hospitals. We demonstrate that a hierarchical non-negative matrix factorization variant which was previously introduced for MP-MRI tumor segmentation gives the best performance in terms of mean Dice-scores for the pathologic tissue classes on both datasets.

Encephalopathy in Wilson disease: copper toxicity or liver failure?

Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology. The most common presentation of Wilson disease (WD) is liver disease and is frequently associated with a wide spectrum of neurological and psychiatric symptoms. The genetic defect in WD leads to copper accumulation in the liver and later in other organs including the brain. In a patient presenting with Wilsonian cirrhosis neuropsychiatric symptoms may be caused either by the metabolic consequences of liver failure or by copper toxicity. Thus, in clinical practice a precise diagnosis is a great challenge. Contrary to HE in neurological WD consciousness, is very rarely disturbed and pyramidal signs, myoclonus dominate. Asterixis and many other clinical symptoms may be present in both disease conditions and are quite similar. However details of neurological assessment as well as additional examinations could help in differential diagnosis.

Magnetic resonance imaging and spectroscopy in hepatic encephalopathy.

Hepatic encephalopathy is a brain alteration associated to liver failure that produces cognitive impairments at long term. Neuroimaging are non-invasive methods for the study of the brain by means of spectroscopy and imaging techniques. These technologies give huge information about cerebral metabolism and water distribution to explore brain pathways involved in the pathogenesis of hepatic encephalopathy. Furthermore, new magnetic resonance implementations such as voxel-based morphometry or resting-state functional magnetic resonance imaging allow studying brain atrophy and neuronal connectivity of the cerebral network involved in the neurocognitive impairments observed in the patients. The development of magnetic resonance technology will generate handy tools for the brain study of liver failure to elucidate the time-course of the pathology and thus to obtain an early diagnosis of cerebral complications.