Long term follow up in 183 high grade meningioma: A single institutional experience.

INTRODUCTION: Meningiomas are usually considered benign lesions, however a proportion of them shows a more aggressive behavior, defined high-grade meningiomas (HGM). Effective medical treatments are lacking, especially at the time of recurrence. METHODS: Through a retrospective analysis, we examined epidemiological, diagnostic, therapeutic, recurrence information and survival data of HGM treated at our institution between 2010 and 2018. RESULTS: 183 patients (105 females and 78 males), with median age of 58 years (25-88), were included; 168 were atypical, 12 anaplastic, 3 rhabdoid. Overall, m-PFS was 4.2 years, and m-OS was 10.3 years. Gross-total resection had a 5-year survival rate of 95% compared with subtotal/partial resection (86% and 67%) (p = 0.002). Higher expression of Ki-67/MIB-1 seems associated with higher risk of death (HR:1.06 with 95% CI, 1.00-1.12, p = 0.03). No statistically significant differences were seen in survival between the group managed with a wait-and-see strategy vs the group treated with RT while a difference on PFS was seen (4.1 years vs 5.2 years p = 0.03). After second recurrence, the most employed treatments were systemic therapies with a very limited effect on disease control. CONCLUSIONS: Data confirmed the aggressive behavior of HGM. The extent of resection seems to correlate with a favorable outcome regardless histological subtypes. The role of RT remains controversial, with no statistically significant impact on OS but a possible role on PFS. Recurrent HGM remains the real challenge, to date no chemotherapies are able to achieve disease control. Future research should focus on biological/molecular predictors in order to achieve a patient-tailored treatment.

Cranial ultrasound is a reliable first step imaging in children with suspected craniosynostosis.

PURPOSE: Skull radiography (SR) and Computed Tomography (CT) are still proposed as the first-line imaging choice for the diagnosis of craniosynostosis (CS) in children with abnormal head shape, but both techniques expose infants to ionizing radiation. Several studies shown that ultrasound may play an important role in the diagnosis of craniosynostosis. The aim of our study is to assess the diagnostic accuracy of cranial ultrasound scan (CUS) and confirm if it is a reliable first step imaging evaluation for the diagnosis of craniosynostosis in newborn. METHOD: A cohort of 196 infants (122/74 males/females), with a mean age of 4 months, clinically suspected to have abnormal closure of cranial sutures, were firstly examined by CUS and then referred to neuroradiologists to perform volumetric CT scan if the suspicion of stenosis was ecographically confirmed; otherwise, a routine follow-up and physical treatment was performed, to observe the evolution of the head shape. RESULTS: Of the 196 children studied by CUS, only two had inconclusive studies due to age limitation (>12 months). Thirty children were diagnosed with cranial synostosis at CUS and verified by CT; all the CUS results were confirmed, except two cases, that were revealed as false positives in the starting phase of the study. Twelve patients with very prominent head deformity and negative CUS underwent CT, which confirmed the CUS results in all of them; one case of closure of both temporal sutures, not studied by CUS, was documented by CT. All the 148 children with poor clinical suspicion and negative CUS underwent just a prolonged clinical follow-up. In all of them, a progressive normalization of head shape was observed, and the craniosynostosis was excluded on a clinical base. CONCLUSIONS: CUS is a highly specific and sensitive imaging technique. In referral centers, expert hands can use it as a reliable first-step screening for infants younger than 1 year, suspected to have a craniosynostosis, thus avoiding unnecessary exposure to ionizing radiation. The "golden age" to obtain the best CUS results is under 6 months of life. Because the method is operator-dependent and there is a learning curve, a case centralization is advisable.

Chiari malformation type 1-related headache: the importance of a multidisciplinary study.

Chiari type 1 Malformation (CM 1) is a structural defect consisting of a displacement of the cerebellar tonsils through the foramen magnum causing obstruction of cerebrospinal fluid (CSF) outflow. CM 1 has a variety of presentation with headache being the most common symptom. The evaluation and treatment of headache related to CM 1 are often difficult, because the pain in the occipital-suboccipital region or headache that is of cough-type suggests symptomatic CM 1, but patients suffering from CM 1 can also report migraine or tension-type headache. In 2015 we started a collaborative project in which our group of neurologists, neurosurgeons and neuroradiologists contribute to create a Chiari Special Outpatient Service; this was set up to provide a multidisciplinary evaluation, treatment and follow-up of patient suffering from CM 1. 201 patients (58 males, 143 females) suffering from CM 1 were multidisciplinary evaluated. Headache characteristics, clinical features, and treatment of patients are discussed. Further progress in multidisciplinary care of headache and CM 1 should be performed to define guidelines.

Early effect of dalfampridine in patients with MS: A multi-instrumental approach to better investigate responsiveness.

BACKGROUND: 4-aminopyridine (4-AP) is a potassium-channel blocker able to enhance walking speed in MS improving the action potentials of demyelinated axons on which internodal potassium channels are exposed. OBJECTIVE: to study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools. METHODS: Clinical (Timed 25-Foot Walk - T25FW, Timed Up-And-Go - TUG), subjective (MS Walking Scale-12 - MSWS-12), neurophysiological (Motor Evoked Potentials - MEPs) and imaging (Diffusion Tensor Imaging - DTI) evaluations were performed before (T0) and after (T1) 14days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI. RESULTS: We found a significant difference between T0 and T1 for T25FW, TUG, MSWS-12 (p≤0.001) in the whole patients' sample (23 subjects, median EDSS 6.0) and decrease of Central Motor Conduction Time and increase of mean Amplitude (Amp) at T1 (p=0.008 and p=0.006). We also recorded a significant difference of T25FW, TUG, MSWS-12 and Amp in clinical responder (CR) patients (CR: amelioration >20% at T25FW). TBSS showed a significant Mean and Radial Diffusivity reduction in the corticospinal tracts (p<0.05) of the whole group of patients; this reduction was also found in the CR subgroup. CONCLUSION: Neurophysiological and neuroradiological parameters were modified in MS patients treated with 4-AP, and most of them reported a subjective improvement of their motor performances after treatment. The use of clinical, subjective, neurophysiological and neuroradiological tools could help to better explore MS patients responsiveness to 4-AP.

Widespread Focal Cortical Alterations in Autism Spectrum Disorder with Intellectual Disability Detected by Threshold-Free Cluster Enhancement.

BACKGROUND AND PURPOSE: In the past decades, a large body of work aimed at investigating brain structural anomalies accrued in autism spectrum disorder. Autism spectrum disorder is associated with intellectual disability in up to 50% of cases. However, only a few neuroimaging studies were conducted in autism spectrum disorder with intellectual disability, and none of them benefited from a nonsyndromic intellectual disability control group. MATERIALS AND METHODS: We performed a voxelwise investigation of the structural alterations in 25 children with autism spectrum disorder with intellectual disability by comparing them with 25 typically developing children and 25 nonsyndromic children with an intellectual disability. Besides a classic voxel-based morphometry statistical approach, the threshold-free cluster enhancement statistical approach was adopted. RESULTS: Classic voxel-based morphometry results did not survive family-wise error correction. The threshold-free cluster enhancement-based analysis corrected for family-wise error highlighted the following: 1) widespread focal cortical anomalies and corpus callosum alteration detected in autism spectrum disorder with intellectual disability; 2) basal ganglia and basal forebrain alteration detected both in autism spectrum disorder with intellectual disability and in nonsyndromic intellectual disability; and 3) differences in the frontocingulate-parietal cortex between autism spectrum disorder with intellectual disability and nonsyndromic intellectual disability. CONCLUSIONS: The present study suggests that the frontocingulate-parietal cortex may be the eligible key region for further investigations aiming at detecting imaging biomarkers in autism spectrum disorder with intellectual disability. The detection of structural alterations in neurodevelopmental disorders may be dramatically improved by using a threshold-free cluster enhancement statistical approach.

Advanced MRI may complement histological diagnosis of lower grade gliomas and help in predicting survival.

MRI grading of grade II and III gliomas may have an important impact on treatment decisions. Occasionally,both conventional MRI (cMRI) and histology fail to clearly establish the tumour grade. Three cMRI features(no necrosis; no relevant oedema; absent or faint contrast enhancement) previously validated in 196 patients with supratentorial gliomas directed our selection of 68 suspected low-grade gliomas (LGG) that were also investigated by advanced MRI (aMRI), including perfusion weighted imaging (PWI), diffusion weighted imaging(DWI) and spectroscopy. All the gliomas had histopathological diagnoses. Sensitivity and specificity of cMRI preoperative diagnosis were 78.5 and 38.5 %, respectively, and 85.7 and 53.8 % when a MRI was included, respectively. ROC analysis showed that cut-off values of 1.29 for maximum rCBV, 1.69 for minimum rADC, 2.1 for rCho/Cr ratio could differentiate between LGG and HGG with a sensitivity of 61.5, 53.8, and 53.8 % and a specificity of 54.7, 43 and 64.3 %, respectively. A significantly longer OS was observed in patients with a maximum rCBV<1.46 and minimum rADC>1.69 (80 vs 55 months, p = 0.01; 80 vs 51 months, p = 0.002, respectively). This result was also confirmed when cases were stratified according to pathology (LGG vs HGG). The ability of a MRI to differentiate between LGG and HGG and to predict survival improved as the number of a MRI techniques considered increased. In a selected population of suspected LGG,classification by cMRI underestimated the actual fraction of HGG. aMRI slightly increased the diagnostic accuracy compared to histopathology. However, DWI and PWI were prognostic markers independent of histological grade.

Intracranial idiopathic hypertension: 1-year follow-up study.

Standard guidelines for ongoing management, as well as definitive data about the long-term course of idiopathic intracranial hypertension (IIH) are not available. The aim of this study was to compare several clinical and instrumental variables as assessed at the time of diagnosis and then after 1 year in a sample of IIH patients. A total of 21 patients were studied. Our results confirmed that headache and TVO are the most frequent symptoms in IIH patients, and that overweight is a very common feature. A trend towards a favorable outcome in patients followed for 1 year and treated by usual medical therapy was found: intracranial pressure was lower at follow-up; improvement of headache and transient visual obscurations, as well as of papilledema, was reported in most patients. On the other hand, neuroradiological findings (such as empty sella, perioptic subarachnoid space distension, narrowing of the transverse sinuses) were substantially stable at follow. These findings may be relevant for future research as far as understanding the role of different clinical and instrumental findings as diagnostic items as well as predictors of outcome in IIH.

Liposomal cytarabine in neoplastic meningitis from primary brain tumors: a single institutional experience.

Neoplastic meningitis (NM) is diagnosed in 1-2 % of patients with primary brain tumors. Standard treatment of NM includes single-agent or combination chemotherapy, with compounds such as methotrexate, thiotepa, and cytarabine (Ara-C) or its injectable, sustained-release formulation Depocyte(®). In this Report, we reported the data of efficacy and tolerability of an intrathecal Depocyte(®) regimen for patients presenting with NM from primary brain tumors. We described 12 patients with NM confirmed at magnetic resonance imaging (MRI) and with a positive cerebrospinal fluid (CSF) cytology. Patients were treated with repeated courses of intrathecal Depocyte(®) (once every 2 weeks for 1 month of induction therapy and as consolidation therapy on a monthly base in responding patients). Twelve patients (10 males and 2 females) were treated by our Institution. The diagnosis of primitive brain tumor was medulloblastoma in six patients, germinoma in two patients, pylocitic astrocytomas with spongioblastic aspects, teratocarcinoma, meningeal melanoma, and ependimoma in the other four patients. The total number of Depocyte(®) cycles ranged from one to nine. In 7/12 patients, there was clinical and/or radiological response after Depocyte(®), and the toxicity was moderate and transient, mainly due to the lumbar puncture procedure. In the two patients with germinoma, we observed a normalization of MRI Imaging and negativization of CSF with disappearance of the tumor cells. OS was 180 days (range 20-300, CI 95 %).

Supratentorial and pontine MRI abnormalities characterize recessive spastic ataxia of Charlevoix-Saguenay. A comprehensive study of an Italian series.

BACKGROUND AND PURPOSE: The autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. The disease, first described in Canadian families from Québec, is characterized by cerebellar ataxia, pyramidal tract involvement and peripheral neuropathy. METHODS: Analysis of SACS gene allowed the identification of 14 patients with ARSACS from 13 unrelated Italian families. Clinical phenotype, gene mutations and magnetic resonance imaging (MRI) findings were analysed. RESULTS: We found 16 novel SACS gene mutations, including a large in-frame deletion. The age at onset was in infancy, but one patient presented the first symptoms at age 32. Progression of the disease was variable, and increased muscle tone was mostly recognized in later stages. Structural MRI showed atrophy of the superior cerebellar vermis, a bulky pons exhibiting T2-hypointense stripes, identified as the corticospinal tract (CST), thinning of the corpus callosum and a rim of T2-hyperintensity around the thalami in 100% of cases. The presence of iron or other paramagnetic substances was excluded. Diffusion tensor imaging (DTI) revealed grossly over-represented transverse pontine fibres (TPF), which prevented reconstruction of the CST at this level (100% of cases). In all patients, significant microstructural alterations were found in the supratentorial white matter of forceps, cingulum and superior longitudinal fasciculus. CONCLUSIONS: Our findings further enlarge the genetic spectrum of SACS mutations and widen the study of clinical phenotype. MRI characteristics indicate that pontine changes and supratentorial abnormalities are diagnostic. The over-representation of TPF on DTI suggests a developmental component in the pathogenesis of the disease.

Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience.

In 1991, a prospective phase II trial was initiated to evaluate the efficacy of treatment for adults with medulloblastoma (MB). After surgery, patients were staged with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology. All patients received three cycles of upfront cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio-spinal radiation therapy. The current article reports on the long-term results from that trial. After a median follow-up of 14.9 years, among a total of 28 adults with MB, the overall progression-free survival and overall survival (OS) rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole group of patients was 11.3 years. The observed toxicity was mainly hematological, with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our small series of patients, the role of combination administration of CDDP + VP16 started before the initiation of radiotherapy in reducing recurrences, particularly distant recurrences, remains unclear. To know whether adding chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.

Basal forebrain involvement in low-functioning autistic children: a voxel-based morphometry study.

BACKGROUND AND PURPOSE: Imaging studies have revealed brain abnormalities in the regions involved in functions impaired in ASD (social relations, verbal and nonverbal communication, and adaptive behavior). We performed a VBM whole-brain analysis to assess the areas involved in autistic children with DD. MATERIALS AND METHODS: Twenty-one developmentally delayed children with ASD (aged 3-10 years) were compared with 21 controls matched for age, sex, and sociocultural background. All ASD cases had been diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, with the Autism Diagnostic Observation Schedule-Generic, and the Autism Diagnostic Interview-Revised. The VBM data, covaried with intelligence quotient, age, and brain volume, were analyzed. RESULTS: ASD patients showed a pattern of regional GM reduction symmetrically affecting the basal forebrain, accumbens nucleus, cerebellar hemispheres, and perisylvian regions, including insula and putamen. Asymmetric involvement of GM was observed in other brain regions functionally connected to the basal forebrain, ie, an area located close to the medial and ventral surface of the frontal lobe. No regional WM differences were observed between the 2 groups. No significant differences between patients and controls were found regarding total brain volume, GM, and WM. CONCLUSIONS: In children with ASD and DD, the novel finding of our VBM study was the demonstration of reduced GM volume in the basal forebrain and the areas connected with it. This system is involved in social behavior, communication, and cognitive skills. Whether the involvement of the basal forebrain is characteristic of ASD or is related to the DD present in our patients needs further investigation.

Cerebral amyloid angiopathy-related inflammation: an emerging disease.

Three elderly patients with, respectively: mild cognitive impairment, severe and progressive neurologic involvement, and focal neurologic deficit, were observed. MRI showed multiple areas of white matter edema, at times partially involving the cortex, in the first two patients, and a single area in the third. Treatment with steroids determined the disappearance of the lesions and clinical amelioration. The key to the diagnosis of cerebral amyloid angiopathy-related inflammation (CAA-ri) was the demonstration, with appropriate MRI sequences, of microbleeds consistent with cerebral amyloid angiopathy (CAA). This diagnosis was supported by genetic analysis of APOE with demonstration of ε4/ε4 genotype, found in about 80% of CAA patients who develop inflammatory changes. In the appropriate clinical setting, MRI demonstration of microbleeds supported by results of genetic analysis of APOE may strongly support the diagnosis of CAA-ri thus avoiding cerebral biopsy.

Decreased diffusivity in the caudate nucleus of presymptomatic huntington disease gene carriers: which explanation?

BACKGROUND AND PURPOSE: The neostriatum is known to be affected in HD. In this work, our aim was to determine whether microstructural and volumetric alterations occur in the neostriatum of presymptomatic HD gene carriers and in patients with early-stage HD. MATERIALS AND METHODS: We studied a group of 15 presymptomatic gene carriers who were far from the estimated symptom onset (16% probability of developing the disease within 5 years), a group of 9 patients with early symptomatic HD, and 2 groups of age-matched controls. Volumetric MR imaging and DWIs were acquired, and statistical analyses were performed on the volumes of the caudate nucleus and putamen and on the corresponding MD measurements. RESULTS: Neostriatal volumes were significantly smaller in both presymptomatic HD gene carriers and symptomatic patients with respect to controls. However, whereas the diffusivity in the caudate nucleus was increased in the symptomatic patients, it was decreased in the presymptomatic gene carriers. CONCLUSIONS: Altered diffusivity and reduced volume of the caudate nucleus in presymptomatic HD gene carriers indicate that the neostriatum is affected well before the onset of symptoms. The observed initial decrease and subsequent increase of MD might be related to the combined effect of increased oligodendroglial population, putatively a developmental abnormality, and incipient neurodegeneration.

Hypothalamic stimulation for trigeminal neuralgia in multiple sclerosis patients: efficacy on the paroxysmal ophthalmic pain.

Trigeminal neuralgia is a disorder characterized by paroxysmal pain arising in one or more trigeminal branches; it is commonly reported in multiple sclerosis. In multiple sclerosis patients the ophthalmic branch may be frequently involved and the risks carried by neurosurgical ablative procedures are higher including major adverse effects such as corneal reflex impairment and keratitis. The objective of this works is to assess the role of posterior hypothalamus neuromodulation in the treatment of trigeminal neuralgia in multiple sclerosis patients. Five multiple sclerosis patients suffering from refractory recurrent trigeminal neuralgia involving all three trigeminal branches underwent deep brain stimulation of the posterior hypothalamus. The rationale of this intervention emerges from our earlier success in treating pain patients suffering from trigeminal autonomic cephalalgias. After follow-up periods that ranged from 1 to 4 years after treatment, the paroxysmal pain arising from the first trigeminal branch was controlled, whereas the recurrence of pain in the second and third trigeminal branches necessitated repeated thermorhizotomies to control in pain in two patients after 2 years of follow-up. In conclusion, deep brain stimulation may be considered as an adjunctive procedure for treating refractory paroxysmal pain within the first trigeminal division so as to avoid the complication of corneal reflex impairment that is known to follow ablative procedures.

Diffusion tensor imaging shows different topographic involvement of the thalamus in progressive supranuclear palsy and corticobasal degeneration.

BACKGROUND AND PURPOSE: In progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), postmortem studies show different topographic involvement of the thalamus, basal ganglia, and their cortical connections. Diffusion tensor imaging (DTI) is an MR imaging technique sensitive to gray and white matter microstructure integrity. This study was performed to determine whether DTI may demonstrate microstructural differences between PSP and CBD, particularly within the thalamus and its cortical connections. MATERIALS AND METHODS: Nine patients with probable PSP, 11 with probable CBD, and 7 controls formed the study group. Apparent diffusion coefficient average (ADC(ave)) and fractional anisotropy (FA) values were measured in regions of interest positioned in the ventrolateral (motor), medial, anterior, and posterior regions of the thalami, basal ganglia, fronto-orbital white matter, cingulum, supplementary motor area (SMA), and precentral and postcentral gyri in patients and controls. RESULTS: In PSP, ADC(ave) values were increased in several areas: the thalamus, particularly in its anterior and medial nuclei; cingulum; motor area; and SMA. FA values were particularly decreased in the fronto-orbital white matter, anterior cingulum, and motor area. In CBD, ADC(ave) was increased in the motor thalamus, in the precentral and postcentral gyri, ipsilateral to the affected frontoparietal cortex, and in the bilateral SMA. FA was mainly decreased in the precentral gyrus and SMA, followed by the postcentral gyrus and cingulum. CONCLUSIONS: In patients with PSP, thalamic involvement was diffuse and prevalent in its anterior part, whereas in CBD involvement was asymmetric and confined to the motor thalamus. DTI may be useful in the differential diagnosis of these 2 parkinsonian disorders.

Engagement of the medial temporal lobe in verbal and nonverbal memory: assessment with functional MR imaging in healthy subjects.

BACKGROUND AND PURPOSE: The hippocampus and parahippocampal gyrus have a central role in the acquisition of new memories. Although functional MR imaging (fMRI) can provide information on the functional status of these brain regions, it has not reached widespread use in the presurgical assessment of patients undergoing temporal lobectomy. We aimed to evaluate whether simple memory-encoding paradigms could be used to elicit robust activations in the hippocampus and parahippocampal gyrus and to determine the lateralization of verbal and nonverbal memory. We also studied the relative contribution of the anterior and posterior portions of these structures. MATERIALS AND METHODS: We conducted this study on 16 healthy subjects by performing event-related fMRI using 3 memory encoding tasks with words, objects, and faces. In addition to a second-level group analysis, region-of-interest (ROI)-based measurements of the signal intensity percent change and of the percentage of activated voxels, determined at 2 thresholds, were performed. ROIs were drawn on the hippocampus and parahippocampal gyrus, divided into anterior and posterior segments. RESULTS: We found overall left-lateralized activation with words, bilateral activation with objects, and right-lateralized activation with faces. In particular, significant hippocampal activations were observed with all 3 categories of stimuli, and the head of the hippocampus was generally more engaged than its body and tail. Data on the signal intensity percent change and percentage of activated voxels are provided for each ROI and task. CONCLUSIONS: The combination of these 3 undemanding memory tasks could be considered, following appropriate validation, as a tool to assess the functional status of the medial temporal lobe in clinical settings.

Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report.

Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte).