Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

The anterolateral triangle as window on the foramen lacerum from transorbital corridor: anatomical study and technical nuances.

OBJECTIVE: Neurosurgical indications for the superior eyelid transorbital endoscopic approach (SETOA) are rapidly expanding over the last years. Nevertheless, as any new technique, a detailed knowledge of the anatomy of the surgical target area, the operative corridor, and the specific surgical landmark from this different perspective is required for a safest and successful surgery. Therefore, the aim of this study is to provide, through anatomical dissections, a detailed investigation of the surgical anatomy revealed by SETOA via anterolateral triangle of the middle cranial fossa. We also sought to define the relevant surgical landmarks of this operative corridor. METHODS: Eight embalmed and injected adult cadaveric specimens (16 sides) underwent dissection and exposure of the cavernous sinus and middle cranial fossa via superior eyelid endoscopic transorbital approach. The anterolateral triangle was opened and its content exposed. An extended endoscopic endonasal trans-clival approach (EEEA) with exposure of the cavernous sinus content and skeletonization of the paraclival and parasellar segments of the internal carotid artery (ICA) was also performed, and the anterolateral triangle was exposed. Measurements of the surface area of this triangle from both surgical corridors were calculated in three head specimens using coordinates of its borders under image-guide navigation. RESULTS: The drilling of the anterolateral triangle via SETOA unfolds a space that can be divided by the course of the vidian nerve into two windows, a wider "supravidian" and a narrower "infravidian," which reveal different anatomical corridors: a "medial supravidian" and a "lateral supravidian," divided by the lacerum segment of the ICA, leading to the lower clivus, and to the medial aspect of the Meckel's cave and terminal part of the horizontal petrous ICA, respectively. The infravidian corridor leads medially into the sphenoid sinus. The arithmetic means of the accessible surface area of the anterolateral triangle were 45.48 ± 3.31 and 42.32 ± 2.17 mm2 through transorbital approach and endonasal approach, respectively. CONCLUSION: SETOA can be considered a minimally invasive route complementary to the extended endoscopic endonasal approach to the anteromedial aspect of the Meckel's cave and the foramen lacerum. The lateral loop of the trigeminal nerve represents a reliable surgical landmark to localize the lacerum segment of the ICA from this corridor. Nevertheless, as any new technique, a learning curve is needed, and the clinical feasibility should be proven.

Post-operative segmental cerebral venous sinus thrombosis: risk factors, clinical implications, and therapeutic considerations.

Cerebral venous sinus thromboses (CVSTs) are rare complications of neurosurgical interventions and their management remains controversial as most of cases appear clinically silent. Here, we analyzed our institutional series of patients with CVSTs evaluating clinical and neuroradiological characteristics, risk factors, and outcome. From the analysis of our institutional PACS, we collected a total of 59 patients showing postoperative CVSTs after supratentorial or infratentorial craniotomies. For every patient, we collected demographics and relevant clinical and laboratory data. Details on thrombosis trend were retrieved and compared along the serial radiological assessment. A supratentorial craniotomy was performed in 57.6% of cases, an infratentorial in 37.3%, while the remaining were a single cases of trans-sphenoidal and neck surgery (1.7%, respectively). A sinus infiltration was present in almost a quarter of patients, and in 52.5% of cases the thrombosed sinus was exposed during the craniotomy. Radiological signs of CVST were evident in 32.2% of patients, but only 8.5% of them developed a hemorrhagic infarct. CVST-related symptoms were complained by 13 patients (22%), but these were minor symptoms in about 90%, and only 10% experienced hemiparesis or impaired consciousness. The majority of patients (78%) remained completely asymptomatic along the follow-up. Risk factors for symptoms occurrence were interruption of preoperative anticoagulants, infratentorial sinuses involvement and evidence of vasogenic edema and venous infarction. Overall, a good outcome defined mRS 0-2 was observed in about 88% of patients at follow-up. CVST is a complication of surgical approaches in proximity of dural venous sinuses. CVST usually does not show progression and courses uneventfully in the vast majority of cases. The systematic use of post-operative anticoagulants seems to not significantly influence its clinical and radiological outcome.

Sex-specific reference values for total, central, and peripheral latency of motor evoked potentials from a large cohort.

Background: Differentiating between physiologic and altered motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) is crucial in clinical practice. Some physical characteristics, such as height and age, introduce sources of variability unrelated to neural dysfunction. We provided new age- and height-adjusted normal values for cortical latency, central motor conduction time (CMCT), and peripheral motor conduction time (PMCT) from a large cohort of healthy subjects. Methods: Previously reported data from 587 participants were re-analyzed. Nervous system disorders were ruled out by clinical examination and magnetic resonance imaging. MEP latency was determined as stimulus-to-response latency through stimulation with a circular coil over the "hot spot" of the First Dorsal Interosseous and Tibialis Anterior muscles, during mild tonic contraction. CMCT was estimated as the difference between MEP cortical latency and PMCT by radicular magnetic stimulation. Additionally, right-to-left differences were calculated. For each parameter, multiple linear regression models of increasing complexity were fitted using height, age, and sex as regressors. Results: Motor evoked potential cortical latency, PMCT, and CMCT were shown to be age- and height-dependent, although age had only a small effect on CMCT. Relying on Bayesian information criterion for model selection, MEP cortical latency and PMCT were explained best by linear models indicating a positive correlation with both height and age. Also, CMCT to lower limbs positively correlated with height and age. CMCT to upper limbs positively correlated to height, but slightly inversely correlated to age, as supported by non-parametric bootstrap analysis. Males had longer cortical latencies and CMCT to lower limbs, as well as longer PMCT and cortical latencies to upper limbs, even when accounting for differences in body height. Right-to-left-differences were independent of height, age, and sex. Based on the selected regression models, sex-specific reference values were obtained for all TMS-related latencies and inter-side differences, with adjustments for height and age, where warranted. Conclusion: A significant relationship was observed between height and age and all MEP latency values, in both upper and lower limbs. These set of reference values facilitate the evaluation of MEPs in clinical studies and research settings. Unlike previous reports, we also highlighted the contribution of sex.

Telomerase inhibition in malignant gliomas: a systematic review.

Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in in vitro and in vivo settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.

Challenging the Pleiotropic Effects of Repetitive Transcranial Magnetic Stimulation in Geriatric Depression: A Multimodal Case Series Study.

BACKGROUND: Although the antidepressant potential of repetitive transcranial magnetic stimulation (rTMS), the pleiotropic effects in geriatric depression (GD) are poorly investigated. We tested rTMS on depression, cognitive performance, growth/neurotrophic factors, cerebral blood flow (CBF) to transcranial Doppler sonography (TCD), and motor-evoked potentials (MEPs) to TMS in GD. METHODS: In this case series study, six drug-resistant subjects (median age 68.0 years) underwent MEPs at baseline and after 3 weeks of 10 Hz rTMS on the left dorsolateral prefrontal cortex. The percentage change of serum nerve growth factor, vascular endothelial growth factor, brain-derived growth factor, insulin-like growth factor-1, and angiogenin was obtained. Assessments were performed at baseline, and at the end of rTMS; psychocognitive tests were also repeated after 1, 3, and 6 months. RESULTS: Chronic cerebrovascular disease was evident in five patients. No adverse/undesirable effect was reported. An improvement in mood was observed after rTMS but not at follow-up. Electrophysiological data to TMS remained unchanged, except for an increase in the right median MEP amplitude. TCD and neurotrophic/growth factors did not change. CONCLUSIONS: We were unable to detect a relevant impact of high-frequency rTMS on mood, cognition, cortical microcircuits, neurotrophic/growth factors, and CBF. Cerebrovascular disease and exposure to multiple pharmacological treatments might have contributed.

Sex differences in mild vascular cognitive impairment: A multimodal transcranial magnetic stimulation study.

BACKGROUND: Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a direct comparison between males and females with mild VCI is lacking. METHODS: Sixty patients (33 females) underwent clinical, psychopathological, functional, and TMS assessment. Measures of interest consisted of: resting motor threshold, latency of motor evoked potentials (MEPs), contralateral silent period, amplitude ratio, central motor conduction time (CMCT), including the F wave technique (CMCT-F), short-interval intracortical inhibition (SICI), intracortical facilitation, and short-latency afferent inhibition, at different interstimulus intervals (ISIs). RESULTS: Males and females were comparable for age, education, vascular burden, and neuropsychiatric symptoms. Males scored worse at global cognitive tests, executive functioning, and independence scales. MEP latency was significantly longer in males, from both sides, as well CMCT and CMCT-F from the left hemisphere; a lower SICI at ISI of 3 ms from the right hemisphere was also found. After correction for demographic and anthropometric features, the effect of sex remained statistically significant for MEP latency, bilaterally, and for CMCT-F and SICI. The presence of diabetes, MEP latency bilaterally, and both CMCT and CMCT-F from the right hemisphere inversely correlated with executive functioning, whereas TMS did not correlate with vascular burden. CONCLUSIONS: We confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.

Intradural extramedullary cervical metastasis from Merkel cell carcinoma: a case report and literature review.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare aggressive primary skin carcinoma with an incidence of 44 cases per 100,000. The natural course of MCC often results in rapid growth and early metastasis. On the other hand, the spinal cord is rarely affected and frequently features the end stage of the disease. The aim of this paper was to clarify the management of patients with spine metastasis from a skin lesion and showed a case-based update. CASE PRESENTATION: A 73-year-old female was admitted to the Neurosurgical Department in December 2021 for a sudden right hemiparesis with bladder dysfunction and a history of cutaneous Merkel cell carcinoma. A magnetic resonance imaging (MRI) of the central nervous system (CNS) showed an intradural-extramedullary right-sided C6-C7 tumor with mass effect and edema of the cervical cord. The patient underwent a C6-C7 laminectomy with microsurgical total resection of the intradural extramedullary lesion. The neuropathological examination identified a metastasis from Merkel cell carcinoma. Nowadays, evidence for spinal metastasis from malignities skin cancer is generally lacking, probably because they are extremely rare. The exact time of life expectancy is controversial, and some clinicians use a cutoff of 3 months to determine whether surgical intervention should be offered, while others advocate at least 6 months of life expectancy. CONCLUSIONS: To the best of our knowledge, we showed the first case of solitary intradural extramedullary cervical spine metastasis from MCC. We recommend to consider metastasis of MCC in the differential diagnosis of spinal metastasis.

Comparison of Effectiveness, Feasibility, Indications, and Limitations of Different Intraoperative Dyes in Spinal Neuro-Oncologic Surgery. A Systematic Review.

BACKGROUND: Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms and their management involves tumors resection in most cases. Regarding the surgical procedure, adequate identification of tumor boundaries is paramount to achieve an extensive tumor resection. Fluorescence image-guided surgery (FIGS) has become an increasing popular intraoperative technique used in spine neuro-oncology surgery. However, evidence is lacking of their usefulness and their safety in spinal tumors. Therefore, the aim of the present study is to give an update of the existing literature and systematically review all studies that focus on the most-used fluorophores (5 aminolevulinic acid [5-ALA], sodium fluorescein, and indocyanine green [ICG]) in IMSCTs. METHODS: Using PubMed and Scopus, we performed a systematic review in accordance with the PRISMA protocol and screened all original studies involving humans treated for neurosurgical conditions and studies evaluating FIGS application in IMSCTs. RESULTS: After the screening phase, 27 articles were found to be relevant. The literature results were grouped according to the used fluorophores, resulting in 3 groups: 5-ALA (10 studies); fluorescein (5 studies), and ICG (12 studies). CONCLUSIONS: In intramedullary tumor surgery, 5-ALA has shown its usefulness in identifying the tumor margins and in searching for residues because of its properties as a tumor-specific metabolic marker. Sodium fluorescein and ICG video angiography have shown promising application in ependymoma and hemangioblastomas surgery, respectively. However, the evolving role of fluorescent dyes in guiding surgical strategies in intramedullary spinal tumor has yet to be shown by randomized clinical trials.

Cerebral hemodynamic changes to transcranial Doppler sonography in celiac disease: A pilot study.

Background: Sonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler sonography. Materials and methods: Montreal Cognitive Assessment (MoCA) and 17-item Hamilton Depression Rating Scale (HDRS) were assessed in 15 newly diagnosed subjects with CD and 15 age-, sex-, and education-matched healthy controls. Cerebral blood flow (CBF) velocities and indices of resistivity (RI) and pulsatility (PI) from the middle cerebral artery (MCA), bilaterally, and the basilar artery (BA) were recorded. We also assessed cerebral vasomotor reactivity (CVR) through the breath-holding test (BHT). Results: Worse scores of MoCA and HDRS were found in patients compared to controls. Although patients showed higher values of CBF velocity from MCA bilaterally compared to controls, both at rest and after BHT, no comparison reached a statistical significance, whereas after BHT both RI and PI from BA were significantly higher in patients. A significant negative correlation between both indices from BA and MoCA score were also noted. Conclusion: These treatment-naïve CD patients may show some subtle CVR changes in posterior circulation, thus possibly expanding the spectrum of pathomechanisms underlying neuroceliac disease and in particular gluten ataxia. Subclinical identification of cerebrovascular pathology in CD may help adequate prevention and early management of neurological involvement.

Atlantoaxial Joint Distraction and Fusion with DTRAX Intra-Articular Cages: A Cadaveric Feasibility Study and Review of the Pertinent Literature.

PURPOSE: Atlantoaxial joint distraction is a key procedure for the treatment of selected patients affected by basilar invagination (BI). In recent years, several authors have reported various techniques of distraction and fixation of the C1-C2 joint using different types of intra-articular spacers, with or without posterior fixation. We review the pertinent literature and propose a feasibility study on the use of a new device for the distraction of the C1-C2 joint aimed to the descent of the dens out of the foramen magnum suggesting its application on selected cases of BI. METHODS: The GL-DTRAX Cervical Cage-SE is a cage approved by the Food and Drug Administration for distraction and fixation of subaxial cervical spine. Five adult cadaveric specimens were dissected surgically to evaluate the feasibility of DTRAX insertion inside the C1-C2 joint through a posterior approach. RESULTS: The cages were uneventfully set into the C1-C2 intra-articular space of all samples without the need to sacrifice C2 nerve roots and ganglia. Postoperative cervical computed tomography scanning confirmed the correct fitting of the devices in every sample. CONCLUSIONS: This cadaveric study highlights the feasibility of the DTRAX cage as a C1-C2 intra-articular device producing a substantial distraction of atlantoaxial complex and suggesting a possible therapeutic role in selected cases of BI.

Change of Clinical and Radiologic Parameters after Minimally Invasive Decompression in Patients with Lumbar Spinal Stenosis. A Prospective Study with Long-term Follow-up.

BACKGROUND: The impact of minimally invasive decompression (MID) techniques on spinopelvic parameters and on the sagittal alignment remains a controversial topic. Here we studied the changes in clinical and radiologic parameters and their relationships in a series of lumbar spinal stenosis (LSS) submitted to MID with a minimum follow-up (FU) of 24 months. METHODS: We prospectively collected clinical and radiologic data of 20 consecutive patients who were evaluated preoperatively, at the 6-month FU, and at the 24-month FU. Visual analog scale (VAS) for back and leg pain, Oswestry disability index (ODI), neck disability index (NDI), sagittal vertical axis (SVA), C7 slope (C7S), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were assessed for each patient. Moreover, the percentage variation of clinical and radiologic factors at the 24-month FU compared with the preoperative factors was calculated to perform correlation studies among these variables. RESULTS: We reported a significant improvement of all clinical parameters. A significant increase of LL and SS and a significant decrease of PT and SVA were observed. The preoperative values of ODI, LL, SS, PT, and SVA significantly affect the 24-month FU values, and the percentage improvement of SVA at the 24-month FU compared with the preoperative values was significantly related to the percentage improvement of LL. CONCLUSIONS: MID is clinically effective in patients with LSS and improves the spinopelvic parameters and the global sagittal balance of the spine. The preoperative spinal alignment affects the spinal alignment at FU. The improvement of SVA was strictly related to the improvement of LL.

Daily mocha coffee intake and psycho-cognitive status in non-demented non-smokers subjects with subcortical ischaemic vascular disease.

Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), mini-mental state examination (MMSE), Stroop Colour-Word Interference Test (Stroop), activities of daily living (ADL0) and instrumental ADL were the outcome measures. Significant differences were observed in higher consumption groups (moderate intake for HDRS; high intake for MMSE and Stroop) compared to the other groups, as well as in age and education. With age, education and coffee used as independent predictors, and HDRS, Stroop and MMSE as dependent variables, a correlation was found between age and both MMSE and Stroop, as well as between education and MMSE and between HDRS and Stroop; coffee intake negatively correlated with HDRS and Stroop. Higher coffee consumption was associated with better psycho-cognitive status among non-smokers with mVCI.

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease.

BACKGROUND: Celiac disease (CD) is now viewed as a systemic disease with multifaceted clinical manifestations. Among the extra-intestinal features, neurological and neuropsychiatric symptoms are still a diagnostic challenge, since they can precede or follow the diagnosis of CD. In particular, it is well known that some adults with CD may complain of cognitive symptoms, that improve when the gluten-free diet (GFD) is started, although they may re-appear after incidental gluten intake. Among the neurophysiological techniques, motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) can non-invasively probe in vivo the excitation state of cortical areas and cortico-spinal conductivity, being also able to unveil preclinical impairment in several neurological and psychiatric disorders, as well as in some systemic diseases affecting the central nervous system (CNS), such as CD. We previously demonstrated an intracortical disinhibition and hyperfacilitation of MEP responses to TMS in newly diagnosed patients. However, no data are available on the central cholinergic functioning indexed by specific TMS measures, such as the short-latency afferent inhibition (SAI), which might represent the neurophysiological correlate of cognitive changes in CD patients, also at the preclinical level. METHODS: Cognitive and depressive symptoms were screened by means of the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively, in 15 consecutive de novo CD patients and 15 healthy controls. All patients were on normal diet at the time of the enrolment. Brain computed tomography (CT) was performed in all patients. SAI, recorded at two interstimulus intervals (2 and 8 ms), was assessed as the percentage amplitude ratio between the conditioned and the unconditioned MEP response. Resting motor threshold, MEP amplitude and latency, and central motor conduction time were also measured. RESULTS: The two groups were comparable for age, sex, anthropometric features, and educational level. Brain CT ruled out intracranial calcifications and clear radiological abnormalities in all patients. Scores at MoCA and HDRS were significantly worse in patients than in controls. The comparison of TMS data between the two groups revealed no statistically significant difference for all measures, including SAI at both interstimulus intervals. CONCLUSIONS: Central cholinergic functioning explored by the SAI of the motor cortex resulted to be not affected in these de novo CD patients compared to age-matched healthy controls. Although the statistically significant difference in MoCA, an overt cognitive impairment was not clinically evident in CD patients. Coherently, to date, no study based on TMS or other diagnostic techniques has shown any involvement of the central acetylcholine or the cholinergic fibers within the CNS in CD. This finding might add support to the vascular inflammation hypothesis underlying the so-called "gluten encephalopathy", which seems to be due to an aetiology different from that of the cholinergic dysfunction. Longitudinal studies correlating clinical, TMS, and neuroimaging data, both before and after GFD, are needed.

Multinodular plexiform tumors of major peripheral nerves: A practical overview.

BACKGROUND AND AIMS: Multinodular/plexiform schwannomas and neurofibromas of major nerves are rare: before surgery, differential diagnosis among these two uncommon variants is challenging. For both forms, surgical removal is recommended in case of progressive growth and worsening of neurological symptoms. Surgery has a higher risk of neurological damage than conventional schwannomas or neurofibromas. In literature, a comparison among these rare tumors is usually limited to the pathological aspect while specific surgical and clinical management indications are lacking. Cutaneous tumors of both forms arising from terminal peripheral nerves' branches might be treated by plastic surgeons while tumors of major nerves remain under neurosurgical competence. Here we report our recent neurosurgical experience on the matter, to furnish useful suggestions for the management of these tumors. METHOD: We analyzed the clinical, radiological, and pathological data in a consecutive case series of plexiform/multinodular nerve tumors operated at our institution in the last five years. RESULTS: In our series, neurofibroma type of plexiform tumors was more frequent than schwannoma type: two sporadic plexiform-multinodular schwannomas (patients 1, and 5) and three multinodular/plexiform Neurofibromatosis familial (Neurofibromatosis 1 / NF-1) (patients 2, 3, and 4). Surgery was complex when major nerves were involved. The early outcome appeared mostly related to the pre-surgical neurological conditions and histological grading. INTERPRETATION: Although sharing some features, multinodular-plexiform schwannomas and neurofibromas have consistent differences from the clinical, surgical and pathological points of view.

Factors associated with cerebrospinal fluid leak after a retrosigmoid approach for cerebellopontine angle surgery.

BACKGROUND: The retrosigmoid approach represents a crucial surgical route to address different lesions in the cerebellopontine angle but cerebrospinal fluid (CSF) leak still remains the most frequent complication after this approach. Here, we analyzed the impact of different factors in CSF leak development after a retrosigmoid approach. Identifying risk factors related to a specific approach may help the surgeon to tailor the perioperative management and to appropriately counsel patients regarding their risk profile. METHODS: We retrospectively reviewed the clinical, surgical, and outcome data of 103 consecutive patients (M/F, 47/56; mean follow-up 35.6 ± 23.9 months) who underwent a retrosigmoid approach for different cerebellopontine angle pathologies and studied the impact of different factors on the occurrence of a CSF leak to univariate and multivariate analysis. RESULTS: Seventy-nine patients (76.7%) were operated for tumors growing in the cerebellopontine angle. Twenty-four patients (23.2%) underwent microvascular decompression to treat a drug-resistant trigeminal neuralgia. Sixteen patients (15.5%) developed CSF leak in the postoperative course of which six underwent surgical revision. Performing a craniectomy as surgical procedure (P = 0.0450) and performing a reopening procedure (second surgery; P = 0.0079) were significantly associated to a higher risk of developing CSF leak. Moreover, performing a reopening procedure emerged as an independent factor for CSF developing on multivariate analysis (P = 0.0156). CONCLUSION: Patients submitted to craniectomy and patients who underwent a second surgery showed an higher CSF leak rate. Ongoing improvement of biomaterial technology may help neurosurgeons to prevent this potentially life-threatening complication.

Intracortical and Intercortical Motor Disinhibition to Transcranial Magnetic Stimulation in Newly Diagnosed Celiac Disease Patients.

BACKGROUND: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. METHODS: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). RESULTS: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. CONCLUSIONS: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.

Unusual case of long survival patient with leptomeningeal carcinomatosis from breast cancer.

Leptomeningeal carcinomatosis (LC) is defined as infiltration of the leptomeninges by metastatic carcinoma and often represents the end stage of cancer disease. In breast cancer, LC is associated with a median survival of approximately 6-8 weeks without specific treatment. It could increase by only few months with personalized treatment plans. Usually, the median time of onset of leptomeningeal spread is 18 months and it is diagnosed in up to 70% of patients with active and progressive systemic disease. We present an uncommon case of LC in a patient with history of breast cancer with a 10 year-disease-free condition and an overall survival after LC diagnosis of 10 months. Central Nervous System (CNS) Magnetic Resonance Imaging (MRI) showed contrast enhancement of medullary cone and cauda. Despite the negativity of cytological analysis of Cerebral-Spinal Fluid (CSF), the patient underwent meningeal and radicular biopsy in November 2019. The neuropathological examination confirmed the diagnosis of LC. The patient was started on the aromatase inhibitor anastrozole. A whole body contrast Computed Tomography (CT) scan at three months follow-up was negative for further disease dissemination. The patient is currently under oncological and radiological follow-up after more than 10 months from diagnosis. Although nowadays diagnosis of LC is prompted by cytological examination of CSF, its negativity should not halt the diagnostic process. In the presence of a high clinical suspicion of LC, we suggest the biopsy of lesion.

Moderate Mocha Coffee Consumption Is Associated with Higher Cognitive and Mood Status in a Non-Demented Elderly Population with Subcortical Ischemic Vascular Disease.

To date, interest in the role of coffee intake in the occurrence and course of age-related neurological and neuropsychiatric disorders has provided an inconclusive effect. Moreover, no study has evaluated mocha coffee consumption in subjects with mild vascular cognitive impairment and late-onset depression. We assessed the association between different quantities of mocha coffee intake over the last year and cognitive and mood performance in a homogeneous sample of 300 non-demented elderly Italian subjects with subcortical ischemic vascular disease. Mini Mental State Examination (MMSE), Stroop Colour-Word Interference Test (Stroop T), 17-items Hamilton Depression Rating Scalfe (HDRS), Activities of Daily Living (ADL), and Instrumental ADL were the outcome measures. MMSE, HDRS, and Stroop T were independently and significantly associated with coffee consumption, i.e., better scores with increasing intake. At the post-hoc analyses, it was found that the group with a moderate intake (two cups/day) had similar values compared to the heavy drinkers (≥three cups/day), with the exception of MMSE. Daily mocha coffee intake was associated with higher cognitive and mood status, with a significant dose-response association even with moderate consumption. This might have translational implications for the identification of modifiable factors for vascular dementia and geriatric depression.