A high-urgency stroke code reduces in-hospital delays in acute ischemic stroke: a single-centre experience.

Timely treatment is essential in acute ischemic stroke as the chances of recovery diminish over time, so efforts are necessary to streamline in-hospital pathways and reduce delays. Here, we analyse the interventions to reduce door-to-needle time in stroke patients suitable for intravenous thrombolysis at the Emergency Department of San Carlo Borromeo Hospital, Milan, Italy. All stroke patients consecutively treated with intravenous thrombolysis at our centre from January 1, 2013 to December 31, 2015 were included in this analysis. The main interventions adopted were (1) continuous education of personnel, (2) reconsideration of blood tests and identify the ones really affecting treatment decision, (3) approval of a new high-urgency Stroke Code activated as soon as the triage nurse comes to know of a potential thrombolysis candidate. Median door-to-needle time progressively decreased from 103 min (iqr 78-120) in 2013, to 92 min (iqr 72-112) in 2014, and to 37 min (iqr 27-58) with the new Stroke Code (p < 0.001) in 2015. Simultaneously, median onset-to-treatment time decreased from 177 min (iqr 142-188) in 2013, to 155 min (iqr 141-198) in 2014, and to 114 min (iqr 86-160) with the new Stroke Code (p < 0.001 and p 0.005, respectively). We did not observe any significant difference in bleeding risks or deaths, whereas the likelihood of favourable outcome (mRS 0-2) increased. Streamlining in-hospital pathways with progressive interventions significantly decreases door-to-needle time and onset-to-treatment time and may contribute to improve stroke outcomes.

Migraine with aura white matter lesions: preliminary data on clinical aspects.

A few clinic-based magnetic resonance imaging studies report an increased risk of signal abnormalities in migraineurs brain's white matter, especially in migraine with aura subjects. A vascular genesis has been hypnotized and migraine with aura was considered an independent risk factor for stroke. Available data of magnetic resonance imaging alterations are often nonspecific and sometimes controversial. The aim of our study is to investigate migraine with aura patients with standardized brain magnetic resonance imaging to detect and to quantify the presence of white matter lesions and to analyze their relation with clinical data. We report preliminary data about first 90 subjects. We did not recognize any clinical aspect in close relationship with these alterations. The only clinical feature that seems to play a role in the presence of alterations is the age, and only in migraineurs women.

Dysregulation of the immune system in Aicardi-Goutières syndrome: another example in a TREX1-mutated patient.

Aicardi-Goutières syndrome (AGS) is a rare genetic encephalopathy characterized by neurological and extraneurological involvement. A clinical overlap between AGS and systemic lupus erythematosus (SLE) has been reported. We describe an AGS patient who developed autoimmune manifestations: thyroiditis, cANCA positivity, antiphospholipid antibodies and cerebral ischemia. This first description of antiphospholipid syndrome in a TREX1-mutated patient further expands the clinical spectrum of AGS. Although the clinical overlap with SLE may indicate common pathogenic mechanisms, the autoimmune manifestations in AGS are so extensive that we suggest they should be considered a clinical feature of the disease, rather than a sign of coexistent SLE.

The Aicardi-Goutières syndrome. Molecular and clinical features of RNAse deficiency and microRNA overload.

Intracellular RNAses are involved in various functions, including microRNA maturation and turnover. Mutations occurring in genes encoding RNAses cause Aicardi-Goutiéres syndrome (AGS). AGS mutations silence RNAse activity, thus inducing accumulation of endogenous RNAs, mainly consisting of short RNAs and microRNAs. Overload of intracellular RNA triggers Toll like receptor-dependent interferon-alpha production in the brain, which in turn activates neurotoxic lymphocytes and inhibits angiogenesis thus inducing the typical clinical phenotype of AGS. However, these pathogenic mechanisms are attenuated after three years of age by the endogenous production of DNAJP58IPK and Cystatin F, which arrest AGS progression. Because RNAses are involved in microRNA turnover, we evaluated the expression of 957 microRNAs in lymphocytes from AGS patients and control patients. Our results indicate that microRNA overload occurs in AGS patients. This upregulation inhibits microRNA turnover impeding the synthesis of the novel microRNAs required for the differentiation and myelination of the brain during the initial period of postnatal life. These pathogenic mechanisms result in AGS, a neurological syndrome characterized by irritability, mild hyperpyrexia, pyramidal and extrapyramidal signs, and spastic-dystonic tetraplegia. Typical cerebrospinal fluid alterations include lymphocytosis and elevated interferon-alpha levels. Brain imaging demonstrates cerebral calcifications, white matter abnormalities, and progressive cerebral atrophy.Thus, evidence exists that mutations silencing intracellular RNases affect microRNA turnover resulting in the severe clinical consequences in the brain characterizing the clinical feature of AGS.

An atypical presentation of diffuse midline pontine glioma in a middle age patient: Case report.

INTRODUCTION: Diffuse midline glioma is a newly WHO defined entity (grade IV) (Louis et al., 2016) which includes diffuse intrinsic pontine glioma (DIPG) reported in pediatric population and, occasionally, in young adults. Here, we present a detailed description of an atypical case of diffuse midline glioma in a 53 years old woman. CASE REPORT: A caucasian woman aged 53 from Ukraine, was referred to another neurological department complaining of 3 months history of progressive postural instability and gait impairment with frequent falling. Magnetic resonance demonstrated two brainstem lesions, hyperintense in FLAIR with "patchy" peripheral enhancement, leptomeningeal and cranial nerves enhancement. CSF was normal. Due to positive antinuclear antibodies test (ANA 1:360), intravenous steroid treatment was administered and reported to initially improve the patient condition. However, the following weeks the lady worsened. Imaging features were unchanged. Because quantiferon test resulted positive, MRI-Spectroscopy showed an inflammatory pattern and MRI perfusion study and brain FDG-PET, were normal, tubercolar granulomatous hypothesis was initially favored. Antitubercular therapy with isoniazid, pyrazinamide, ethambutol and rifampicin was started without any clinical improvement. Hence, the biopsy was proposed. The procedure revealed a diffuse midline pontine glioma. Considering the advanced stage of the disease, radiotherapy was not indicated. Patient died after eight months from the onset of neurological disturbances. CONCLUSION: Our case shows that diffuse midline glioma is a CNS tumor not limited to young population but occurring also in middle aged patients with an insidious pattern. We therefore recommend to perform biopsy at very early stages in patients with atypical brainstem lesions.

POMT1 and POMT2 mutations in CMD patients: a multicentric Italian study.

Mutations in POMT1 and POMT2 genes were originally identified in Walker-Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with alpha-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with alpha-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought.

Migraine with aura and white matter abnormalities: Notch3 mutation.

The authors report on an Italian family with eight affected members who show autosomal dominant migraine with prolonged visual, sensory, motor, and aphasic aura. These symptoms are associated with white matter abnormalities on brain MRI. All living affected members carry a Notch3 mutation (Arg153Cys) previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). White matter abnormalities occur in a variable percentage of the general migraine population; CADASIL should be suspected in migraineurs with prolonged atypical aura and white matter abnormalities.

Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis.

Randomized Controlled Trials have not let established the best pharmacological management of Acute Disseminated Encephalomyelitis (ADEM). High dose steroids are usually employed with good results, but in a few cases the clinical outcome is poor. In other patients, particularly those affected by the site restricted ADEM variants (myelitis), the disease shows a recurrent course resembling that of Multiple Sclerosis. We present here five patients, 3 of them affected by classic disseminated encephalomyelitis and 2 by a post infectious myelitis, which showed a good response to intravenous immunoglobulin (IVIg) after steroid treatment failure. In our report high dose steroids administration was substantially uneffective in all but one case, who showed a good response only during the first episode. On the contrary IVIg injection (0,4 gr/kg/day) produced a marked functional improvement in all patients starting within the first five days of drug administration and reaching a maximum within three weeks. One patient experienced a good effect nothwithstanding a steady dysability. In all cases, clinical evidence was supported by MRI controls showing improving posttreatment changes.

Transsynaptic degeneration of lateral geniculate bodies in blind children: in vivo MR demonstration.

PURPOSE: To investigate signal alterations in the thalamic lateral geniculate bodies of blind patients compatible with transsynaptic degeneration of these nuclei caused by pregeniculate or postgeniculate interruption of the visual pathway. METHODS: Six patients were selected from a group of blind children in our care. Four had cerebral palsy caused by periventricular leukomalacia, one had infantile neuroaxonal dystrophy, and one had Chiari I malformation and hydrocephalus, which was worsened by bilateral ischemic lesions of the occipital lobes. MR examinations (obtained at 0.5 T) were reviewed retrospectively by two neuroradiologists, with particular attention to the visual pathway. RESULTS: Symmetric, focal areas of T2 prolongation were found at the precise site of the lateral geniculate bodies. CONCLUSION: Anterograde (pregeniculate) and retrograde (postgeniculate) transsynaptic degeneration of the second neurons of the visual pathway produce alterations in MR signal.

Ganglioneuroblastoma of the spinal cord.

We report a case of ganglioneuroblastoma of the spinal cord in a 42-year-old man. MR examination was nonspecific, and the diagnosis was made from histologic findings. The MR picture was that of an intramedullary, mainly solid tumor with a central necrotic or cystic portion. The clinical picture and course were also nonspecific.

Cerebral visual impairment in periventricular leukomalacia: MR correlation.

PURPOSE: To evaluate the involvement of central visual pathways in cases of periventricular leukomalacia, and to correlate the neuroradiologic findings with the degree of visual acuity. METHODS: The MR brain examinations of 27 preterm children affected by cerebral palsy resulting from periventricular leukomalacia and without significant ophthalmologic lesions were reviewed retrospectively to search for possible involvement of the optic radiations and/or of the calcarine cortex. The data were compared with the degree of visual acuity estimated by means of the Teller Acuity Cards test. RESULTS: Seventeen (63%) of the 27 patients had cerebral visual impairment, which correlated strongly with MR lesions. Quantitative reduction and signal hyperintensity of the peritrigonal white matter and atrophy of the calcarine cortex were present in the more severe cases. In two blind patients, an altered MR signal was detected in the lateral geniculate bodies. CONCLUSION: This study clearly establishes a relationship between specific MR findings and visual impairment in children with periventricular leukomalacia. The finding of hyperintensity in the lateral geniculate bodies was interpreted as an axonal reaction. MR imaging is useful for detecting potential visual impairment and for improving clinical diagnosis.

Body composition and energy expenditure in Duchenne muscular dystrophy.

OBJECTIVE: To investigate the relationship between resting energy expenditure (REE) and body composition in Duchenne Muscular Dystrophy (DMD). DESIGN: An observational study. SETTING: University Research Centre. SUBJECTS: Nine Duchenne children (age range 6-12 y), mean relative weight 128%, agreed to undergo the investigation and all of them completed the study; INTERVENTIONS: Assessment of body composition (total body fat and skeletal muscle mass) by magnetic resonance imaging and resting energy expenditure by indirect calorimetry. MAIN OUTCOME MEASURES: Fat mass (FM; kg and percentage weight), fat-free mass (FFM; kg and percentage weight), muscle mass (kg and percentage weight), resting energy expenditure (kJ/kg body weight and kJ/kg fat-free mass). RESULTS: : In Duchenne children fat mass averages 32% and total skeletal muscle mass 20% of body weight. Resting energy expenditure per kg of body weight falls within the normal range for children of the same age range, while when expressed per kg of FFM is significantly higher than reference values. No relationship was found between REE and total skeletal muscle mass. CONCLUSIONS: Our results do not demonstrate a low REE in DMD boys; on the contrary REE per kg of FFM is higher than normal, probably due to the altered FFM composition. We suggest that the development of obesity in DMD children is not primarily due to a low REE but to other causes such as a reduction in physical activity and or overfeeding.

Measurement of skeletal muscle mass in Duchenne muscular dystrophy: use of 24-h creatinine excretion.

Creatinine concentration in 24-h urine has been proposed as an indirect measure of body skeletal muscle mass (SMM). We attempted to correlate urinary creatinine levels with SMM in eight patients with Duchenne muscular dystrophy, a progressive disease in which the degree of muscle wasting parallels the rate of progression. Magnetic resonance imaging and a newly developed protocol for image analysis were used for the measurement of SMM. The patients ate a creatine-free diet for the week before urine collection. Creatinine was measured with an enzymatic-colorimetric method. Mean (+/-SD) SMM value was 5.4+/-2.5 kg and urine creatinine levels 205.8+/-96.4 mg/day. Daily urinary creatinine excretion did not correlate with SMM. The simple creatinine determination in urine cannot predict SMM in Duchenne muscular dystrophy.

[Neuroradiology of spontaneous cerebral hematomas]. / Neuroradiologia degli ematomi intracerebrali spontanei.

Computed Tomography plays a fundamental role in the diagnosis of spontaneous intracerebral haemorrhage, providing important informations relevant to prognosis and therapy. Therefore angiography should be planned on the basis of the CT finding and of some clinical data such as age, presence of risk factors, etc. Also the neurosurgical approach, besides clinical status, will depend on the neuroradiological evaluation.

Cognitive and neuroradiological findings in myotonic dystrophy.

Cognitive functions were investigated in 37 patients with myotonic dystrophy (MD) and correlated with clinical and neuroradiological variables. The whole cognitive performance was at a low-average level; in about 1/3 of the subjects, in fact, the scores at the neuropsychological tests were below the normal range. There was a consistent trend for patients with inheritance on maternal side to perform worse on Wechsler verbal score and to present cerebral atrophy. In 7 out of 12 subjects focal white matter lesions were found at nuclear magnetic resonance. The significance of these findings and its relation to cognitive performance are discussed.

[Indications for x-rays of the skull and cervical spine: an open question]. / Indicazioni alle radiografie del cranio e della colonna cervicale: problematica aperta.

During the first six months of 1990, a study was carried out on a group of patients examined at the Neuroradiology Department of a Neurological Institute for skull and cervical spine X-rays. Kind of disturbances, the examination prescribed and patients' places of origin were taken into consideration. We studied 174 patients: 108 suffering from headache, 28 from cervical arthrosis, and the others from miscellaneous diseases. Male/Female ratio (M/F) was lower in the group affected by headache; the age was more advanced in the group affected by cervical arthrosis. Skull X-rays were usually normal in headache patients; cervical X-rays were not informative in cervical arthrosis patients. We can conclude that only through a different relationship between the prescribing physician and the Radiologist it will be possible to approach the justification and optimization criteria of medical radiological exposure.

[High-dose carboplatin superselective intraarterial chemotherapy in advanced head and neck cancer]. / La chemioterapia intraarteriosa neo-adiuvante superselettiva con carboplatino ad alte dosi nei tumori avanzati cervico-facciali.

Advances in vascular radiology techniques for superselective transfemoral arterial infusion prompted us to evaluate the effects of high-dose rapid regional carboplatin infusion for patients with advanced head and neck squamous cell carcinomas. Twenty untreated patients received three infusions of carboplatin (300-350 mg/m2) every 2 weeks with this method. All the infusions were performed without any complication. Treatment was well tolerated, with moderate (Grade 1-3 WHO) local toxicity (stomatitis, dermatitis and alopecia) and minimal (Grade 1-2 WHO) myelosuppression. The total response index (complete response plus partial response) was 94% for primary tumors and 50% for neck metastases. Neoadjuvant chemotherapy employing superselective rapid infusion of high-dose carboplatin is a feasible, relatively nontoxic, effective technique and may have important applications in multimodality therapy of untreated patients with advanced head and neck cancer.

Congenital muscular dystrophies with cognitive impairment. A population study.

BACKGROUND: Cognitive impairment has been reported in a significant proportion of patients with congenital muscular dystrophies (CMD), generally associated with brain changes. OBJECTIVES: The aim of this study was to establish 1) the overall prevalence of CMD and cognitive impairment in the Italian population; 2) the frequency of individual genetically defined forms; and 3) the presence of distinct phenotypes not associated with mutations in the known genes. METHODS: We included all patients with CMD and cognitive impairment followed in all the Italian tertiary neuromuscular centers. Clinical, brain MRI, and morphologic data were collected. Genetic screening of the known genes was performed according to clinical and muscle biopsy findings. RESULTS: Ninety-two of the 160 (58%) patients with CMD followed in our centers had cognitive impairment. alpha-Dystroglycan (alpha-DG) reduction on muscle biopsy was found in 73/92 (79%), with 42/73 carrying mutations in the known genes. Another 6/92 (7%) showed a laminin alpha2 deficiency on muscle biopsy and 5 of the 6 carried mutations in LAMA2. The remaining 13/92 (14%) patients had normal alpha-DG and laminin alpha2 expression on muscle. CONCLUSIONS: This is the first population study establishing the prevalence of CMD and cognitive impairment and providing a classification on the basis of clinical, MRI, and genetic findings. We also showed that cognitive impairment was not always associated with alpha-DG or laminin alpha2 reduction or with structural brain changes.

Aicardi-Goutieres syndrome: neuroradiologic findings and follow-up.

BACKGROUND AND PURPOSE: To date, few studies have focused specifically on imaging findings in Aicardi-Goutières syndrome (AGS). We set out to evaluate retrospectively neuroradiologic data from a large sample of patients with AGS, focusing on the pattern of white matter abnormalities and the temporal evolution of the cerebral involvement to establish the radiologic natural history of the disease. MATERIALS AND METHODS: Thirty-six patients, 18 girls and 18 boys, were included. All had a clinical diagnosis of AGS, genetically confirmed in 31 of them. For every subject, we reviewed at least 1 CT and 1 MR imaging study; 19 (52.7%) had multiple examinations. In all, we reviewed 109 examinations. Clinical-neuroradiologic comparisons were analyzed by using the chi(2) test. RESULTS: Calcifications were found in all subjects, mainly in the basal ganglia, lobar white matter, and dentate nuclei. Abnormal white matter was present in all the subjects, showing 2 patterns of distribution: diffuse in 18 (50%) and an anteroposterior gradient in 18 (50%). Cystic areas were observed in the temporal and/or frontal lobes in 12/36 patients (33.3%). A correlation was found between early age at onset and severity of the leukoencephalopathy in the frontal (P = .024) and temporal (P = .034) regions. A significant degree of cerebral atrophy was found in 31/36 subjects (86.1%). The neuroradiologic presentation remained substantially stable with time. CONCLUSIONS: The different neuroradiologic presentations of AGS are here outlined for the first time in a large sample of patients. These findings may facilitate more precise and earlier diagnosis of this rare but probably underdiagnosed syndrome.