The Present and Future of Optic Pathway Glioma Therapy.

Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.

Nummular headache: a case report of remission following ketogenic diet and botulinum toxin type A injections.

Nummular headache is an unusual facial pain disorder with no evidence-based therapy recommendations. The ketogenic diet is an alternative therapy that demonstrated to be effective in migraineurs, but it was never used in the setting of nummular headache. We describe a 58-years old female patient with nummular headache successfully treated with a 6-months ketogenic diet and botulinum toxin type A injections. Ketogenic diet could be an effective alternative/complementary therapy in nummular headache patients although more studies are needed to confirm our results.

Predictive risk factors of phenoconversion in idiopathic REM sleep behavior disorder: the Italian study "FARPRESTO".

Most patients with idiopathic REM sleep behavior disorder (iRBD) will develop an overt α-synucleinopathy over time, with a rate of phenoconversion of 73.5% after 12 years from diagnosis. Several markers of phenoconversion were identified; however, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without standardized data collection methods. The risk FActoRs PREdictive of phenoconversion in idiopathic REM sleep behavior disorder: the Italian STudy (FARPRESTO) is a multicentric longitudinal retrospective and prospective study with a cohort of incident (prospective recruitment) and prevalent (retrospective recruitment) iRBD patients, whose primary aim is to stratify the risk of phenoconversion, through the systematic collection by means of electronic case report forms of different biomarkers. Secondary aims are to (1) describe the sociodemographic and clinical characteristics of patients with iRBD; (2) collect longitudinal data about the development of α-synucleinopathies; (3) monitor the impact of iRBD on quality of life and sleep quality; (4) assess the correlation between phenoconversion, cognitive performance, and loss of normal muscle atony during REM sleep; (5) identify RBD phenotypes through evaluating clinical, biological, neurophysiological, neuropsychological, and imaging biomarkers; and (6) validate vPSG criteria for RBD diagnosis. The FARPRESTO study will collect a large and harmonized dataset, assessing the role of different biomarkers providing a unique opportunity for a holistic, multidimensional, and personalized approach to iRBD, with several possible application and impact at different levels, from basic to clinical research, and from prevention to management. The FARPRESTO has been registered at clinicaltrials.gov (NCT05262543).

Ketogenic Diet in the Treatment of Gliomas and Glioblastomas.

In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between healthy and neoplastic cells: neoplastic cells divert their metabolism to anaerobic glycolysis (Warburg effect), they alter the normal mitochondrial functioning, and they use mainly certain amino acids for their own metabolic needs, to gain an advantage over healthy cells and to lead to a pro-oncogenetic effect. Several works in literature speculate which are the molecular targets of KD used against cancer. The following different mechanisms of action will be explored in this review: metabolic, inflammatory, oncogenic and oncosuppressive, ROS, and epigenetic modulation. Preclinical and clinical studies on the use of KD in CNS tumors have also increased in recent years. An interesting hypothesis emerged from the studies about the possible use of a ketogenic diet as a combination therapy along with chemotherapy (CT) and radiotherapy (RT) for the treatment of cancer. Currently, however, clinical data are still very limited but encouraging, so we need further studies to definitively validate or disprove the role of KD in fighting against cancer.

Multisensory mental representation in covid-19 patients and the possibility of long-lasting gustatory and olfactory dysfunction in the CNS.

Gustatory (GD) and olfactory (OD) dysfunctions are the most frequent neurological manifestations of COVID-19. We used mental imagery as an experimental psychological paradigm to access olfactory and gustatory brain representations in 80 Italian COVID-19 adult patients (68.75% reported both OD and GD). COVID-19 patients with OD + GD have a significantly and selectively decreased vividness of odor and taste imagery, indicating that COVID-19 has an effect on their chemosensory mental representations. OD + GD length and type influenced the status of mental chemosensory representations. OD + GD were become all COVID-19 negative at the time of testing. Data suggest that patients are not explicitly aware of long-term altered chemosensory processing. However, differences emerge when their chemosensory function is implicitly assessed using self-ratings. Among patients developing OD + GD, self-ratings of chemosensory function (taste, flavor) were significantly lower as compared to those who did not. At the level of mental representation, such differences can be further detected, in terms of a reduced ability to mentally activate an odor or taste mental image. Our study shows that COVID-19 infection not only frequently causes hyposmia and dysgeusia, but that may also alter the mental representations responsible for olfactory and gustatory perception.

Multisensory mental imagery of fatigue: Evidence from an fMRI study.

Functional imaging experimental designs measuring fatigue, defined as a subjective lack of physical and/or mental energy characterizing a wide range of neurologic conditions, are still under development. Nineteen right-handed healthy subjects (9 M and 10 F, mean age 43.15 ± 8.34 years) were evaluated by means of functional magnetic resonance imaging (fMRI), asking them to perform explicit, first-person, mental imagery of fatigue-related multisensory sensations. Short sentences designed to assess the principal manifestations of fatigue from the Multidimensional Fatigue Symptom Inventory were presented. Participants were asked to imagine the corresponding sensations (Sensory Imagery, SI). As a control, they had to imagine the visual scenes (Visual Imagery, VI) described in short phrases. The SI task (vs. VI task) differentially activated three areas: (i) the precuneus, which is involved in first-person perspective taking; (ii) the left superior temporal sulcus, which is a multisensory integration area; and (iii) the left inferior frontal gyrus, known to be involved in mental imagery network. The SI fMRI task can be used to measure processing involved in mental imagery of fatigue-related multisensory sensations.

Electroencephalographic Evaluation for Early Diagnosis of Limbic Encephalitis.

Limbic encephalitis (LE) is an inflammation of structures of limbic system. It may be an autoimmune disease or secondary to a neoplasia. Onset is subacute within a few weeks and clinical presentation is characterized by behavioral changes, psychiatric symptoms, short-term memory loss, and epileptic seizures. Diagnosis is typically set after a magnetic resonance imaging (MRI) scan, revealing hyperintensity in limbic structures on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences or detection of antineuronal antibodies; EEG aspecific alterations on temporal areas usually match with MRI and laboratory findings. Specific diagnostic criteria are still under debate. We describe a case presenting with EEG alterations before MRI ones.A 36-year-old woman came to our attention for a first generalized tonic-clonic seizure, several episodes of likely epigastric auras and memory loss. Her clinical history was unremarkable. Neurological examination and brain MRI with gadolinium were normal. Electroencephalographic (EEG) recordings showed theta activity and sharp elements in frontotemporal regions. Therapy with levetiracetam 1000 mg/day was started, but she had another generalized seizure and episodes of epigastric auras increased to 10 per day. After 2 months, another cerebral MRI revealed areas of swelling and signal alteration in deep left temporal areas, especially in hippocampal and parahippocampal gyrus. A spectroscopic evaluation revealed decreased N-acetyl aspartate peak and increased choline and myo-inositol peaks in left frontotemporal areas. These findings were consistent with LE. Cerebrospinal fluid (CSF) analysis was normal; viral serology and onconeuronal antibodies on CSF and blood were negative. Patient was treated with high-dosage steroids, with improvement in memory, epileptic seizures and auras. A third MRI revealed no signal alterations.In conclusion, the clinical picture initially did not meet accepted diagnostic criteria for LE. Effective steroid therapy was consequently delayed. With this case report we would emphasize diagnostic relevance of EEG alterations early in suspected LE in order to start immunosuppressive therapy as soon as possible.

Lacosamide for the treatment of epilepsy.

INTRODUCTION: Epilepsy is one of the most common neurological disorders. Despite the development of new antiepileptic drugs (AEDs), ∼ 30% of epilepsy patients experience recurrent seizures and even more experience side effects. Therefore, there is still need for new AEDs with enhanced effectiveness and tolerability. AREAS COVERED: The article is based on a search using PubMed, including articles published between 1999 and 2013. It is focused on the pharmacokinetic, pharmacological and clinical data of lacosamide (LCM) for the treatment of epilepsy. EXPERT OPINION: Along with favorable tolerability and pharmacokinetic profiles, LCM has been demonstrated to significantly reduce seizure frequency in patients with partial-onset seizures when prescribed as adjunctive treatment at doses of 200 and 400 mg/day. LCM has a unique mechanism of action, selectively enhancing slow inactivation of voltage-gated sodium channels. Its mechanism of action could be exploited to reduce the percentage of pharmacoresistant patients. Although LCM is not FDA approved for treatment of status epilepticus, it has demonstrated promising preliminary results. Large prospective studies are needed to verify these. In addition, the results of ongoing trials will help to confirm if LCM could be used as a monotherapy regimen in the treatment of partial-onset seizures and generalized tonic-clonic seizures.

Gabapentin enacarbil, a gabapentin prodrug for the treatment of the neurological symptoms associated with disorders such as restless legs syndrome.

Restless Legs Syndrome (RLS) is a sleep-related movement disorder characterized by an urge to move the legs accompanied by unpleasant symptoms. Dopaminergic agents currently represent the first-line therapy for RLS. However, some patients are unable to continue with this pharmacological approach in the long term because of augmentation or other adverse events. Limited studies with the anticonvulsant/analgesic agent gabapentin have demonstrated that this drug might be useful in the treatment of primary and uremic RLS. Unfortunately, gabapentin has an unfavorable pharmacokinetic profile characterized by a dose-dependent bioavailability. Gabapentin enacarbil, a prodrug of gabapentin, is currently being developed by XenoPort Inc/Astellas Pharma Inc/GlaxoSmithKline plc in order to overcome this limitation. In vitro and in vivo studies have demonstrated that gabapentin enacarbil provides a dose-proportional exposure to gabapentin when orally administered. Gabapentin enacarbil has proved to be beneficial in treating RLS symptoms in several phase II and III clinical trials. In addition, these trials have demonstrated that gabapentin enacarbil is safe and well tolerated, causing transient and mild or moderate adverse events. Gabapentin enacarbil is an interesting compound, which is potentially useful in treating RLS patients who report severe adverse events under dopaminergic agents. The author concludes that additional studies are required in order to better assess the efficacy and safety of gabapentin enacarbil on RLS.

Sensory gating deficit assessed by P50/Pb middle latency event related potential in Alzheimer's disease.

Sensory gating is defined as the brain's ability to inhibit repetitive and irrelevant incoming sensory stimuli and is supposed to be related to cholinergic transmission. Indeed, Alzheimer's disease (AD) is characterized by a cholinergic deficit that is believed to be involved in cerebral cortex hyperexcitability and short latency afferent inhibition deficit. Therefore, a sensory gating deficit may be supposed present in AD within the frame of cortex hyperexcitability and loss of cortex modulation of sensory inputs. The authors investigated whether a sensory gating deficit may be present in AD and whether this deficit may be related to the presence of neuropsychiatric symptoms (NPS) and reversed by donepezil treatment. Sensory gating was evaluated using a paired-stimulus auditory P50 event-related potential paradigm. Eighteen drug-naïve probable AD patients (mean age 76.1 years; SD 5.6 years; 13 females and 5 males) and 15 healthy elderly controls (mean age 74.2 years; SD 5.4 years; 10 females and 5 males) were recruited. Sensory gating was evaluated in AD patients before starting therapy and after 1 and 3 months of donepezil treatment. Auditory P50 sensory gating was impaired in AD patients but no correlation was found between gating deficit and NPS. Moreover, AD patients displayed increased P50 amplitude when compared with healthy elderly subjects. Donepezil treatment did not improve P50 sensory gating in AD patients but decreased P50 amplitude. Patients with AD displayed an augmented P50 amplitude, in accordance with previous studies, suggesting increased cortex excitability. Donepezil does not affect P50 sensory gating but reduces P50 amplitude. Donepezil may induce P50 amplitude reduction by means of enhanced dopamine release. Indeed, it has been demonstrated that donepezil induces dopamine release "in vitro." The findings suggest that AD patients have a sensory gating impairment but the link with both NPS and the cholinergic deficit is doubtful.