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

Improved Brain Pathology and Progressive Peripheral Neuropathy in a 15 Year Old Survivor of Infantile Krabbe Disease Treated With Umbilical Cord Transplantation

ObjectiveKrabbe disease is a fatal leukodystrophy caused by deficiency in galactocerebrosidase enzyme activity. The only currently available therapy is hematopoietic stem cell transplantation with bone marrow or umbilical cord blood (UCBT), which leads to increased lifespan and functional abilities when performed in the preclinical stage. While stabilization of white matter disease has been seen on serial MRI studies, neuropathological changes following transplantation have not been documented so far.Materials and MethodsWe report the first postmortem examination of a 15-year-old female patient with infantile Krabbe disease after UCBT in infancy.ResultsIn contrast to an untreated Krabbe disease brain, which showed severe myelin and oligodendrocyte loss with occasional globoid cells, the transplanted brain displayed markedly improved myelin preservation, but not reaching normal myelination levels. Consistent with the transplanted patient’s clinical presentation of pronounced deficits in gross motor skills, corticospinal tracts were most severely affected. No globoid cells or evidence of active demyelination were observed in the central nervous system, indicative of at least partially successful functional restoration. This was corroborated by the identification of male donor-derived cells in the brain by in situ hybridization. Unlike the observed disease stabilization in the central nervous system, the patient experienced progressive peripheral neuropathy. While diminished macrophage infiltration was seen postmortem, peripheral nerves exhibited edema, myelin and axon loss and persistent Schwann cell ultrastructural inclusions.ConclusionUmbilical cord blood transplantation was able to alter the natural disease progression in the central but less so in the peripheral nervous system, possibly due to limited cross-correction of Schwann cells

The diagnosis of posterior reversible encephalopathy syndrome

[no abstract available

Imaging findings in primary central nervous system vasculitis

Primary central nervous system vasculitis (PCNSV) is a rare primary vasculitis limited to the brain and spinal cord. It can affect any age group, but has a predilection for subjects aged 40 to 60 years without clear gender predominance. Clinical manifestations are nonspecific, including headache, non-focal neurological features and, less frequently, focal neurological signs. Brain biopsy is the diagnostic gold standard, but may be falsely negative when unaffected tissue is sampled. In addition, brain biopsy carries a small but significant risk of serious complications. Imaging procedures are a key part of the workup of PCNSV patients. They can be used to document the extent and type of lesions, to gauge response to treatment, and sometimes as surrogates for brain biopsy. Magnetic resonance is extremely sensitive but non-specific. The most common findings are multiple bilateral ischaemic lesions often involving white and grey matter. Conventional or magnetic resonance angiography (MRA) typically shows segmental narrowing and dilation in multiple cerebral arteries. However, atypical findings have also been described both with magnetic resonance and angiography. This review discusses the state-of-the-art of current imaging techniques in the workup of PCNSV patients and highlights future prospects

18F-Fluorodeoxyglucose positron emission tomography for the assessment of myositis: a case series

To establish whether 18FFluorodeoxyglucose (FDG) positron emission computerised tomography (FDG-PET/CT) might reveal active disease in patients with myositis

Infliximab for the treatment of Neuro-Behçet's disease: a case series and review of the literature

Behçet's disease (BD) is a vasculitis in which the hallmark lesions are oral and often genital ulcers. Involvement of parenchymal central nervous system (neuro-Behçet's) is a serious complication commonly characterized by brainstem and/or basal ganglia lesions. To date, treatment of neuro-Behçet's remains largely empirical, and may not adequately control the disease. Serum tumor necrosis factor α (TNFα) levels are increased in active BD, suggesting a role for TNFα in disease pathogenesis. Clinically, significant improvement of various BD manifestations has been reported with TNFα blockade. However, evidence for the efficacy of TNFα blockers in the treatment of neuro-Behçet's is scant. We present 8 patients with neuro-Behçet's who responded favorably to infliximab therapy and review the relevant literature