Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report

<p>Abstract</p> <p>Background</p> <p>Management of glioblastoma multiforme (GBM) has been difficult using standard therapy (radiation with temozolomide chemotherapy). The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI). Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the <it>MGMT </it>gene promoter.</p> <p>Methods</p> <p>Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein) ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone) was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET).</p> <p>Results</p> <p>After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy.</p> <p>Conclusion</p> <p>This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed to evaluate the efficacy of restricted ketogenic diets, administered alone or together with standard treatment, as a therapy for GBM and possibly other malignant brain tumors.</p

An unexpected evolution of symptomatic mild middle cerebral artery (MCA) stenosis: asymptomatic occlusion

<p>Abstract</p> <p>Background</p> <p>The intracranial localization of large artery disease is recognized as the main cause of ischemic stroke in the world, considering all countries, although its global burden is widely underestimated. Indeed it has been reported more frequently in Asians and African-American people, but the finding of intracranial stenosis as a cause of ischemic stroke is relatively common also in Caucasians. The prognosis of patients with stroke due to intracranial steno-occlusion is strictly dependent on the time of recanalization. Moreover, the course of the vessel involvement is highly dynamic in both directions, improvement or worsening, although several data are derived from the atherosclerotic subtype, compared to other causes.</p> <p>Case description</p> <p>We report the clinical, neurosonological and neuroradiological findings of a young woman, who came to our Stroke Unit because of the abrupt onset of aphasia during her work. An urgent neurosonological examination showed a left M1 MCA stenosis, congruent with the presenting symptoms; magnetic resonance imaging confirmed this finding and identified an acute ischemic lesion on the left MCA territory. The past history of the patient was significant only for a hyperinsulinemic condition, treated with metformine, and a mild overweight. At this time a selective cerebral angiography was not performed because of the patient refusal and she was discharged on antiplatelet and lipid-lowering therapy, having failed to identify autoimmune or inflammatory diseases. Within 1 month, she went back to our attention because of the recurrence of aphasia, lasting about ten minutes. Neuroimaging findings were unchanged, but the patient accepted to undergo a selective cerebral angiography, which showed a mild left distal M1 MCA stenosis.</p> <p>During the follow-up the patient did not experienced any recurrence, but a routine neurosonological examination found an unexpected evolution of the known MCA stenosis, i.e. left M1 MCA occlusion. Neuroradiological imaging did not identify new lesions of the brain parenchyma and a repeated selective cerebral angiography confirmed the left M1 MCA occlusion.</p> <p>Conclusions</p> <p>Regardless of the role of metabolic and/or inflammatory factors on the aetiology of the intracranial stenosis in this case, the course of the vessel disease was unexpected and previously unreported in the literature at our knowledge.</p

Unbalanced metalloproteinase-9 and tissue inhibitors of metalloproteinases ratios predict hemorrhagic transformation of lesion in ischemic stroke patients treated with thrombolysis: Results from the MAGIC study

Background Experimentally, metalloproteinases (MMPs) play a detrimental role related to severity of ischemic brain lesions. Both MMPs activity and function in tissues reflect the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs). We aimed to evaluate the role of MMPs/TIMPs balance in the setting of rtPA treated stroke patients Methods Blood was taken before and 24-hours after rtPA from 327 patients (mean age 68 years, median NIHSS 11) with acute ischemic stroke. Delta median values of each MMP/TIMP ratio [(post rtPA MMP/TIMP-baseline MMP/TIMP)/(baseline MMP/TIMP)] were analyzed related to symptomatic intracranial hemorrhage (sICH) according to NINDS criteria, relevant hemorrhagic transformation (HT) defined as hemorrhagic infarction type 2 or any parenchimal hemorrhage, stroke subtypes (according to Oxfordshire Community Stroke Project) and 3-month death. The net effect of each MMP/TIMP ratio was estimated by a logistic regression model including major clinical determinants of outcomes Results Adjusting for major clinical determinants, only increase in MMP9/TIMP1 and MMP9/TIMP2 ratios remained significantly associated with sICH (odds ratio [95% confidence interval], 1.67 [1.17 – 2.38], p = 0.005; 1.74 [1.21 – 2.49], p=0.003 respectively). Only relative increase in MMP9/TIMP1 ratio proved significantly associated with relevant HT (odds ratio [95% confidence interval], 1.74 [1.17 – 2.57], p=0.006) with a trend towards significance for MMP9/TIMP2 ratio (p=0.007).Discussion Our data add substantial clinical evidence about the role of MMPs/TIMPs balance in rtPA treated stroke patients. These results may serve to generate hypotheses on MMPs inhibitors to be administered together with rtPA in order to counteract its deleterious effect

A qualitative model for aggregation and diffusion of β\beta -amyloid in Alzheimer’s disease

In this paper we present a mathematical model for the aggregation and diffusion of Aβ amyloid in the brain affected by Alzheimer's disease, at the early stage of the disease. The model is based on a classical discrete Smoluchowski aggregation equation modified to take diffusion into account. We also describe a numerical scheme and discuss the results of the simulations in the light of the recent biomedical literature

Automatic identification of Mild Cognitive Impairment through the analysis of Italian spontaneous speech productions

This paper presents some preliminary results of the OPLON project. It aimed at identifying early linguistic symptoms of cognitive decline in the elderly. This pilot study was conducted on a corpus composed of spontaneous speech sample collected from 39 subjects, who underwent a neuropsychological screening for visuo - spatial abilities, memory, language, executive functions and attention. A rich set of linguistic features was extracted from the digitalised utterances (at phonetic, su prasegmental, lexical, morphological and syntactic levels) and the statistical significance in pinpointing the pathological process was measured. Our results show remarkable trends for what concerns both the linguistic traits selection and the automatic classifiers building

Automatic identification of Mild Cognitive Impairment through the analysis of Italian spontaneous speech productions

This paper presents some preliminary results of the OPLON project. It aimed at identifying early linguistic symptoms of cognitive decline in the elderly. This pilot study was conducted on a corpus composed of spontaneous speech sample collected from 39 subjects, who underwent a neuropsychological screening for visuo - spatial abilities, memory, language, executive functions and attention. A rich set of linguistic features was extracted from the digitalised utterances (at phonetic, su prasegmental, lexical, morphological and syntactic levels) and the statistical significance in pinpointing the pathological process was measured. Our results show remarkable trends for what concerns both the linguistic traits selection and the automatic classifiers building

Should we screen for cognitive decline and dementia?

a b s t r a c t Due to increased life expectancy, the prevalence of cognitive decline related to neurodegenerative diseases and to non-neurological conditions is increasing in western countries. As with other diseases, the burden might be reduced through personalized interventions delivered at early stages of the disease. Thus, there is an increasing demand, from both social and healthcare systems, for instruments and strategies to recognize cognitive decline, and possibly distinguish the precursor of serious neurodegeneration from &quot;benign senile forgetfulness&quot; or the temporary consequences of illness or trauma. However, this goal faces both technical and ethical issues. In this article we deal with the following: (i) re-definition of cognitive decline and its relationship with frailty definitions, starting from the recent work of international consensus groups for presymptomatic Alzheimer disease recognition; (ii) ethical problems concerning anonymous and personalized cognitive screening and the need for appropriate counselling; (iii) the need for more sensitive and specific tools to detect and distinguish pathological levels of cognitive decline and delineate the contribution of non-pathological decline to accumulated frailty impacts and (iv) the potential of the language domain and spontaneous speech analyses

Should we screen for cognitive decline and dementia?

Due to increased life expectancy, the prevalence of cognitive decline related to neurodegenerative diseases and to non-neurological conditions is increasing in western countries. As with other diseases, the burden might be reduced through personalized interventions delivered at early stages of the disease. Thus, there is an increasing demand, from both social and healthcare systems, for instruments and strategies to recognize cognitive decline, and possibly distinguish the precursor of serious neurodegeneration from "benign senile forgetfulness" or the temporary consequences of illness or trauma. However, this goal faces both technical and ethical issues. In this article we deal with the following: (i) re-definition of cognitive decline and its relationship with frailty definitions, starting from the recent work of international consensus groups for presymptomatic Alzheimer disease recognition; (ii) ethical problems concerning anonymous and personalized cognitive screening and the need for appropriate counselling; (iii) the need for more sensitive and specific tools to detect and distinguish pathological levels of cognitive decline and delineate the contribution of non-pathological decline to accumulated frailty impacts and (iv) the potential of the language domain and spontaneous speech analyses

Should we screen for cognitive decline and dementia?

Due to increased life expectancy, the prevalence of cognitive decline related to neurodegenerative diseases and to non-neurological conditions is increasing in western countries. As with other diseases, the burden might be reduced through personalized interventions delivered at early stages of the disease. Thus, there is an increasing demand, from both social and healthcare systems, for instruments and strategies to recognize cognitive decline, and possibly distinguish the precursor of serious neurodegeneration from "benign senile forgetfulness" or the temporary consequences of illness or trauma. However, this goal faces both technical and ethical issues. In this article we deal with the following: (i) re-definition of cognitive decline and its relationship with frailty definitions, starting from the recent work of international consensus groups for presymptomatic Alzheimer disease recognition; (ii) ethical problems concerning anonymous and personalized cognitive screening and the need for appropriate counselling; (iii) the need for more sensitive and specific tools to detect and distinguish pathological levels of cognitive decline and delineate the contribution of non-pathological decline to accumulated frailty impacts and (iv) the potential of the language domain and spontaneous speech analyses