Magnetic resonance metrics to evaluate the effect of therapy in amyotrophic lateral sclerosis: the experience with edaravone.

BACKGROUND: Edaravone was approved as a new treatment for amyotrophic lateral sclerosis (ALS), although there are different opinions on its effectiveness. Magnetic resonance (MRI) measures appear promising as diagnostic and prognostic indicators of disease. However, published studies on MRI using to monitor treatment efficacy in ALS are lacking. PURPOSE: The objective of this study was to investigate changes in brain MRI measures in patients treated with edaravone. METHODS: Thirteen ALS patients assuming edaravone (ALS-EDA) underwent MRI at baseline (T0) and after 6 months (T6) to measure cortical thickness (CT) and fractional anisotropy (FA) of white matter (WM) tracts. MRI data of ALS-EDA were compared at T0 with those of 12 control subjects (CS), and at T6 with those of 11 ALS patients assuming only riluzole (ALS-RIL), extracted from our ALS cohort using a propensity-score-matching. A longitudinal MRI analysis was performed in ALS-EDA between T6 and T0. RESULTS: At T0, ALS-EDA showed a cortical widespread thinning in both hemispheres, particularly in the bilateral precentral gyrus, and a reduction of FA in bilateral corticospinal tracts, in comparison to CS. Thinning in bilateral precentral cortex and significant widespread reduction of FA in several WM tracts were observed in ALS-EDA at T6 compared to T0. At T6, no significant differences in MRI measures of ALS-EDA versus ALS-RIL were found. CONCLUSIONS: Patients treated with edaravone showed progression of damage in the motor cortex and several WM tracts, at a six-month follow-up. Moreover, this study showed no evidence of a difference between edaravone and riluzole.

"Less is better"-always true?

OBJECTIVE: The aim of the study is to try to explain what an overtreatment is and which ones are the possible risks related to an excess of simplification in the medical practice, through the description of an emblematic clinical case. METHODS: In the present article, we report the case of a female patient aged 57 who complained about lower back pain and crural neuralgia and had a lumbar and sacral magnetic resonance imaging performed in the Department of Neuroradiology in Bari showing suspicious repetitive bone lesions; therefore, the patient underwent several medical procedures and laboratory exams which ended with a surgical removal of a left L3-L4 foraminal disc herniation and a bone biopsy. RESULTS: When it was finally possible to exclude any other diseases including thyroid neoplasms, a "reassuring" osteoporosis diagnosis has been made since the lesions were likely to be degenerative and the patient underwent menopause 7 years ago. However, the multiplicity of the lesions of the vertebrae and of the pelvic bones as well as their signal could not be ignored, so that a close magnetic resonance imaging follow-up has been recommended. CONCLUSIONS: The present case is therefore a good example of overtreatment which may lead to delicate questions, investigating any possible mistakes in the diagnosis procedure as well as the role that defensive medicine is playing nowadays on medical procedures and the economic impact that all this can have on our healthcare system. In the end, we may ask ourselves: is "less" better or is "more" always "more?"

Recurrent Painful Ophthalmoplegic Neuropathy and Oculomotor Nerve Schwannoma: A Pediatric Case Report with Long-Term MRI Follow-Up and Literature Review.

Background: Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine (OM), is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. The age of presentation is most often during childhood or adolescence. MRI has a central role in the assessment of the RPON, especially to distinguish orbital, parasellar, or posterior fossa lesions that mimic symptoms of RPON. Actually, oculomotor nerve tumors may be masquerade as RPON so that MRI follow-ups are required to detect the possibility of tumor etiology. Case presentation: We report a 16-year-old boy with a 7-year follow-up and multiple brain MRI data, previously diagnosed as OM. The last brain MRI, performed during an acute phase of oculomotor paresis with ipsilateral headache, showed a nodular lesion described as schwannoma of III cranial nerve. Then, we reviewed the literature on OM and RPON in pediatric age with a focus on brain MRI findings. Conclusions: This review highlights the important role of serial brain MRIs in the long-term follow-up of RPON, especially in the cases with childhood onset, in order to not delay the diagnosis of a possible oculomotor nerve schwannoma.

Convexal subarachnoid hemorrhage and acute ischemic stroke: a border zone matter?

BACKGROUND: Convexal subarachnoid hemorrhage (c-SAH) is an infrequent condition with variable causes. c-SAH concomitant to acute ischemic stroke (AIS) is even less frequent, and the relationship between the two conditions remains unclear. METHODS: Between January 2016 and January 2018, we treated four patients who were referred to our stroke unit with ischemic stroke and concomitant nontraumatic c-SAH. The patients underwent an extensive diagnostic workup, including digital subtraction angiography (DSA). RESULTS: All four patients developed acute focal neurological symptoms with restricted MRI diffusion in congruent areas. In three of the patients, infarcts were in a border zone between the main cerebral arteries and c-SAH was nearby. The fourth patient showed a small cortical infarct, and c-SAH was in a border zone territory of the contralateral hemisphere. An embolic source was discovered or strongly suspected in all cases. One patient was treated with intravenous thrombolysis, but this treatment was not related to c-SAH. None of the four patients showed microbleeds or further cortical siderosis, thus excluding cerebral amyloid angiopathy. In addition, DSA did not show signs of vasculitis, reversible cerebral vasoconstriction syndrome, or intracranial arterial dissection. CONCLUSIONS: We proposed the embolism or hemodynamic changes of the border zone arterioles as a unifying pathogenetic hypothesis of coexisting c-SAH and AIS.

Pain and Muscles Properties Modifications After Botulinum Toxin Type A (BTX-A) and Radial Extracorporeal Shock Wave (rESWT) Combined Treatment.

BACKGROUND AND OBJECTIVE: Spasticity (most common disability in upper motor neuron syndrome or UMNS) caused an inability of patients' to perform daily activities and a decrease inquality of life. One of the promising methods nowadays, but still not widely used in everyday practice, for spasticity reduction is extracorporeal shock wave. The aim of this study was to evaluate the objective clinical effects of combined treatment botulinum toxin type A and radial Extracorporeal Shock Wave Therapy in spasticity post stroke. METHODS: We considered 30 subjects (14 female and 16 male) with post stroke spasticity of Biceps Brachii, Superficial Flexor Digitorum, Gastrocnemius Medialis and Lateralis and we divided patients into two groups (group A received botulinum toxin injection and physiotherapy while group B received botulinum toxin injection, rESWT and physiotherapy). Assessments were performed before treatment (t0), after 1 (t1), 2 (t2) e 3 (t3) months using Modified Ahworth Scale, Visual Analogical Scale for pain and MyotonPro® device (to assessed myometric evaluation of muscles tone and stiffness). RESULTS: Visual Analogical Scale, Modified Ahworth Scale, muscles tone and stiffness statistically decreased until t3 in the group A and in the group B, but the differences between the two groups were significant at the t1 only. CONCLUSION: Radial Extracorporeal Shock Wave Therapy could be an effective physical treatment aimed at the reduction of upper and lower limbs spasticity and could lead to the improvement of trophic conditions of the spastic muscles in post-stroke.

MR evaluation of encephalic leukoaraiosis in sudden sensorineural hearing loss (SSNHL) patients.

Epidemiological evidence suggests a strict correlation between sudden sensorineural hearing loss (SSNHL) and cerebrovascular disorders. Leukoaraiosis represents a diffuse alteration of the periventricular and subcortical white matter. The aim of our study was to verify if the presence of white matter hyperintensity (WMH) was higher in patients affected by SSNHL compared to controls and evaluate the correlation between WMH and the cardiovascular risk factors, hearing level, and the response to therapy in SSNHL patients. The study group included 36 subjects affected by unilateral SSNHL. Thirty-six age- and sex-matched normal subjects with a negative history of SSNHL were used as controls. All patients underwent magnetic resonance imaging (MRI) (1.5 Tesla GE Signa) and the extent of leukoaraiosis was assessed with the Fazekas scale. The results of the present study demonstrate a high prevalence of WMH in SSNHL patients compared to controls confirming the hypothesis of a vascular impairment in SSNHL patients. The higher recovery rate in patients with greater periventricular white matter hyperintensity (PWMH) may suggest a vascular etiology that is still responsive to medical treatment. We aim to expand both the number of patients and the controls to avoid the limitation of the still small number to warrant solid scientific conclusions.

Inoperable Giant Growth Hormone-secreting Pituitary Adenoma: Radiological Aspects, Clinical Management and Pregnancy Outcome.

BACKGROUND AND OBJECTIVE: Giant pituitary adenomas (GPAs) are benign tumours with a diameter ≥ 4 cm [1]. They can cause symptoms and signs due to the possible hyper-secretion of one or more pituitary hormones, and involvement of the surrounding structures whereas the compression of the pituitary itself can lead to hypopituitarism. METHODS: We report on a young woman with acromegaly due to an inoperable giant GH-secreting pituitary adenoma extending to right cavernous sinus, right orbital cavity, ethmoid, right maxillary sinus, sphenoid sinus, clivus and right temporal fossa, in which medical treatment with Octreotide- LAR was able to promptly relieve headache and bilateral hemianopsia due to optic chiasm involvement, improve acromegaly symptoms and, over the time, control tumor expansion, improving fertility and therefore allowing the patient to become pregnant. RESULTS: Octreotide-LAR therapy was withdrawn during pregnancy and the patient did not experience complications and gave birth to a healthy son. On magnetic resonance, the size of the tumor at the end of pregnancy and in the subsequent follow up was not increased. CONCLUSION: The history we report, therefore, confirms previous experiences reporting a possible favourable outcome of pregnancy in patients affected by acromegaly and adds further information about the behaviour of giant pituitary tumors in patients underwent pregnancy.

Frontal lobe metabolic alterations in autism spectrum disorder: a 1H-magnetic resonance spectroscopy study.

PURPOSE: Recently, neuroimaging studies were performed using 1H-magnetic resonance spectroscopy (1H-MRS), revealing a quantitative alteration of neurochemicals (such as neurotransmitters and metabolites) in several brain regions of patients with autism spectrum disorder (ASD). The involvement of the frontal lobe in the neurobiology of ASD has long been documented in the literature. Therefore, the aim of this study was to analyze the alterations of N-acetylaspartate/creatine (NAA/Cr) and choline/Cr (Cho/Cr) ratios in the frontal lobe subcortical white matter (WM) in ASD patients, in order to reveal any alteration of metabolites that might be the expression of specific clinical features of the disorder. PATIENTS AND METHODS: An 1H-MRS study of the frontal lobe subcortical WM was performed in 75 children with ASD and in 50 age-matched controls to evaluate the functional activity of this brain region. RESULTS: NAA/Cr and Cho/Cr ratios were significantly altered in ASD, compared to control subjects. Moreover, in the ASD group, NAA/Cr was significantly lower in patients with a cognitive impairment. CONCLUSION: Results from this study confirm the existence of brain metabolites' alterations in frontal lobe WM in children with ASD, supporting the relevance of this brain region in the clinical expressions of this disorder, including its role in the cognitive impairment. Further 1H-MRS investigations will allow to comprehensively explain the relationship between metabolic alteration in a specific brain region and specific clinical features of ASD.

The pedicle instrumentation and percutaneous elevation (Pi.Pe): a new cementless surgical technique in type A post-traumatic vertebral fractures.

PURPOSE: To investigate if bone substitutes are strictly necessary to restore the vertebral body height and improve the clinical outcome, in patients with thoracolumbar or lumbar AO type A post-traumatic vertebral fractures, managed with balloon kyphoplasty combined with posterior screw and rod system. METHODS: 105 patients with post-traumatic thoracolumbar spine fracture were recruited. At baseline, the patients underwent a CT and an MRI of the spine. Clinical evaluation was performed, using the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI), at baseline, 48 h after surgery, at 3-month follow-up (FU), 6-month FU, 48 h after the instrumentation removal and at 24-month FU. At each FU, VK, regional kyphosis (RK), central wall (MH/PH) and anterior wall (AH/PH) heights were assessed on lateral spine X-rays. At 6-month FU, a CT scan of the spine was performed to investigate the fracture healing. The posterior instrumentation was removed 7 months after surgery (range 6-10 months). RESULTS: A significant reduction of mean VAS (p < 0.05) and ODI (p < 0.05) was observed after surgery; no impairment of these scores was observed after the instrumentation removal. A significant correction of VK, RK, AH/PH and MH/PH was recorded after surgery; no significant changes of these values were noticed at subsequent FU. After the instrumentation removal, only an RK impairment was recorded, but it was not significant. CONCLUSIONS: PMMA or bone substitutes are not necessary to keep the reduction of the endplate obtained with the balloon tamp, when BK is performed in the association with posterior percutaneous pedicle screws instrumentation. These slides can be retrieved under Electronic Supplementary Material.

Efficacy and Non Invasive Treatment of Sialorrhea in the Goldenhar Syndrome.

BACKGROUND AND OBJECTIVE: Goldenhar syndrome (ocular-auricular-vertebral syndrome), a rare congenital condition arising from defects in the first and second brachial arches, consists in clinical variety of features ranging from facial abnormalities, ear-eye abnormalities, vertebral defects and congenital heart problems and severe obstructive sleep apnea. Due to craniofacial abnormalities, patients presents mechanical obstructive phenomena and sialorrhea that cause prone position, language's fastening, use of nasopharyngeal cannulas and tracheal intubation. METHODS: In this article, we report a case of a 16 years old child affected by Goldenhar syndrome and sialorrhea to demonstrate improvement of the daily patient management, through inoculations of botulinum toxin type A. Due to severe sialorrhea which caused tracheobronchial daily aspirations, the caregivers used an external aspirators. RESULTS: In the first infiltration (August 2016) the parotid and submandibular glands bilaterally were inoculated with incobotulinum toxin type A (Xeomin®, Merz Pharma) with dosages of 5 UI for each of them, for a total of 20 UI without clinical efficacy (no quantitative and qualitative saliva reducing during 3 months). In the second (November 2016) and third (February 2017) infiltrations each parotid and each submandibular glands were injected with a (dosage of 7 UI and 5 UI respectively (total of 24 UI of incobotulinumtoxin A) with important clinical results (saliva production and tracheo-bronchial aspirations reduced). CONCLUSION: Therefore, botulinum toxin type A could be a good and non invasive treatment of sialorrhea in Goldenhar syndrome to improve oral hygiene and daily patient management.

The Role of Neurohypophyseal Hormones Vasopressin and Oxytocin in Neuropsychiatric Disorders.

BACKGROUND AND OBJECTIVE: Although the neurohypophyseal hormones vasopressin (VP) and oxytocin (OT) are mostly known for their role respectively in antidiuresis, and in labour, lactation and maternal behavior, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact with each other facilitating shifts between positive socially- oriented and defensive states. In fact, VP amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas OT reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of these neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. The aim of this paper is to review the literature relating to the role played by neurohypophyseal hormones in neuropsychiatric disorders. METHODS: We analyzed the best of published literature dealing with the relationships between neurohypophyseal hormones and neuropsychiatric conditions like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on December 2017. RESULTS: Several studies indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if conflicting data have been reported, several mechanisms may be involved in these behavioral diseases, such as differences in aminoacid sequence and peptide biological activity, neurotransmission and genetic disorders involving OT and VP receptors. CONCLUSION: The involvment of VP and OT in neurpopsychiatric disorders can support a possible beneficial therapy with OT or with VP antagonists. The target may be obtained using effective drug delivery methods as well as the association with other drugs.

Langerhans cell histiocytosis of the maxillae in a child treated only with chemotherapy: a case report.

BACKGROUND: Langerhans cell histiocytosis is a sporadic disease caused by an uncontrolled pathogenic clonal proliferation of dendritic cells that have Langerhans cell characteristics. New treatment protocols provided by the HISTSOC-LCH-III (NCT00276757) trial show an improvement in the survival of children with langerhans cell histiocytosis. CASE PRESENTATION: We report a case of Langerhans cell histiocytosis, which presented as an osteolytic lesion of the left pre-maxillae enclosing the deciduous incisor and canine in a 7-month-old white Italian boy. He was treated with chemotherapy. He achieved complete remission after 7 months and after 24 months no signs of recurrence were observed. CONCLUSIONS: As a result of this treatment, anesthetic sequelae and loss of teeth were avoided; in addition, we prevented a loss of the vertical dimension of occlusion.

Vertebral Bone Marrow Edema (VBME) in Conservatively Treated Acute Vertebral Compression Fractures (VCFs): Evolution and Clinical Correlations.

STUDY DESIGN: Prospective observational study. OBJECTIVE: To assess (1) the evolution of vertebral bone marrow edema (VBME) in patients with A1 vertebral compression fractures (VCFs) conservatively treated and (2) the relationship between VBME and clinical symptoms, evaluated as Visual Analogue Scale (VAS) back pain and Oswestry Disability Index (ODI). SUMMARY OF BACKGROUND DATA: VBME is a marker of acute-subacute vertebral fractures. Little is known about the evolution of VBME in conservatively managed VCFs, as well as its clinical meaning. METHODS: 82 thoracic or lumbar VCFs (21 post-traumatic; 61 osteoporotic VCFs), type A1 according to the AOSpine thoracolumbar spine injury classification system, in 80 patients were treated with C35 hyperextension brace for 3 months, bed rest for the first 25 days. Patients with osteoporotic fractures also received antiresorptive therapy and vitamin D supplementation. At 0 (T0), 30 (T1), 60 (T2), and 90 (T3) days, patients underwent magnetic resonance imaging evaluation and clinical evaluation, using VAS for pain and ODI.The paired t test was used to compare changes within groups at each follow-up versus baseline. The unpaired t test after ANOVA (analysis of variance) was used to compare the 2 groups at each follow-up.The association between VBME area, VAS score, and ODI score was analyzed by the Pearson correlation test. The tests were 2-tailed with a confidence level of 5%. RESULTS: A significant VBME mean area, VAS, and ODI scores reduction was recorded at 60 and 90-days follow-ups versus baseline. A positive correlation between VBME reduction and clinical symptoms improvement (VAS and ODI scores improvement) was found in both traumatic and osteoporotic VCFs. CONCLUSION: In benign A1 VCFs conservatively managed, VBME slowly decreases in the first 3 months of magnetic resonance imaging follow-up. This VBME reduction is related to clinical symptoms improvement. LEVEL OF EVIDENCE: 4.

Erdheim-Chester disease: a systematic review.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent myelomonocytic precursors or in tissue-resident histiocytes. It encompasses a spectrum of disorders ranging from asymptomatic bone lesions to multisystemic, life-threatening variants. We reviewed all published reports of histologically-confirmed ECD and explored clinical, radiological, prognostic and therapeutic characteristics in a population of 448 patients, including a unique patient from our Department. To find a clinically relevant signature defining differentiated prognostic profiles, the patients' disease features were compared in relation to their CNS involvement that occurred in 56% of the entire population. Diabetes insipidus, visual disturbances, pyramidal and extra-pyramidal syndromes were the most recurrent neurological signs, whereas concomitant pituitary involvement, retro-orbital masses and axial lesions in the presence of symmetric bilateral osteosclerosis of long bones depicted the typical ECD clinical picture. Patients with CNS infiltration showed a lower occurrence of heart involvement and a higher incidence of bone, skin, retro-peritoneal, lung, aortic and renal infiltration. No difference in the therapeutic algorithm was found after stratification for CNS involvement. A better understanding of the disease pathogenesis, including BRAF deregulation, in keeping with improved prognostic criteria, will provide novel suggestions for the management of ECD.

(18)F-FDG PET/CT contribution to diagnosis and treatment response of rhino-orbital-cerebral mucormycosis.

OBJECTIVE: Mucormycosis is an infection caused by mycetes mucorales, emerged as a life-threatening infection associated with severe morbidity and high mortality. Conventional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) are usually performed to assess mucormycosis extension, but they may present insufficiencies in their performance. CASE PRESENTATION: We present the case of a 13 years old patient with diagnosis of rhino-orbital-cerebral mucormycosis (RCM) who performed head MRI and [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) both for the infection spread assessment and for the early evaluation of response to systemic amphotericin-B treatment. CONCLUSION: This case suggests that (18)F-FDG PET/CT could be considered as a valuable tool for the initial staging of RCM when compared with MRI and should be performed as soon as possible after the first clinical suspicion of this disease. In addition (18)F-FDG PET/CT may also be useful for the assessment of response to treatment.

Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease.

Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children.

OBJECTIVE: To evaluate the clinical features in a large cohort of pediatric patients with genetically confirmed hereditary hemorrhagic telangiectasia (HHT) and to identify possible predictors of arteriovenous malformation (AVM) onset or clinical significance. STUDY DESIGN: Prospective cross-sectional survey of all children subjected to screening for AVMs in the multidisciplinary HHT center. All patients proved to be carriers of endoglin mutations or activin A receptor type-II-like kinase 1 mutations, defined as HHT1 and HHT2, respectively. A full clinical-radiological protocol for AVM detection was adopted, independent from presence or absence of AVM-related symptoms. RESULTS: Forty-four children (mean age, 10.3 years; range, 1-18) were subjected to a comprehensive clinical-radiologic evaluation. This investigation disclosed cerebrovascular malformations in 7 of 44 cases, pulmonary AVMs in 20 of 44 cases, and liver AVMs in 23 of 44 cases. Large visceral AVMs were found in 12 of 44 children and were significantly more frequent in patients with HHT1. Only large AVMs were associated with symptoms and complications. CONCLUSIONS: Children with HHT have a high prevalence of AVMs; therefore, an appropriate clinical and radiological screening protocol is advisable. Large AVMs can be associated with complications in childhood, whereas small AVMs probably have no clinical risk.