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Orbital floor fractures can cause functional disorders such as limitation of ocular motility. The dysfunction of the extrinsic muscles was studied with the Hess-Lancaster test; although we expected a large percentage of inferior rectus muscle dysfunction, the results showed 52% superior rectus muscle dysfunction. In light of these results, we began testing five patients with functional deficits evidenced by the Hess-Lancaster test with magnetic resonance imaging to assess the change in thickness of the affected muscle compared to the contralateral healthy muscle during standardized eye movements. This investigation showed an increase in the size of the inferior rectus muscle on the affected side during the fraction of time when the patient was asked to look up, probably due to post-traumatic fibrosis. According to our hypothesis, muscle thickness would condition the correct release of the inferior rectus muscle to such an extent that it would also influence the contraction of the superior rectus muscle, which would then be deficient. Based on our experience, a multidisciplinary approach and longer follow-up with thorough investigations should be considered for patients with orbital floor fractures. Furthermore, our results suggest the need for early surgical treatment, in contrast to current guidelines that aim to delay restorative surgery. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to increase awareness of the hemorrhagic presentation of intracranial meningiomas in the emergency department and present clues for neuroradiological diagnosis, which is crucial for pertinent management. We described the prevalence of hemorrhage in a large population of meningioma patients, with emphasis on clinical presentation, computed tomography (CT), magnetic resonance (MR), and digital subtraction angiography (DSA) findings. Methods: This retrospective analysis has been performed at two reference institutions between January 2002 and December 2015, and includes 1304 patients with histologically proven newly diagnosed intracranial meningioma. Clinical features and neuroradiological findings of intracranial meningiomas presenting with hemorrhage have been reviewed. Results: Twenty-four patients (1.8%, 16 females, 8 males, age range: 29–88 years) were found to have spontaneous hemorrhagic onset of the newly diagnosed meningioma. A sudden onset occurred in 23/24 patients. Sixteen patients showed isolated intralesional hemorrhage, four had subdural hematomas, and the remaining four presented combined intralesional and subarachnoid (n = 2) or intraventricular (n = 2) hemorrhages. In 13 patients, CT showed both the hemorrhage and the meningioma. In the other 11 patients, diagnosis was achieved by emergency or early surgery (n = 5), MRI (n = 5), and DSA (n = 1). Conclusions: The presence of an underlying meningioma has to be considered in the differential diagnosis of spontaneous intracranial hemorrhage, although this is a rare event. CT, MRI, and occasionally DSA were useful to obtain the diagnosis; however, in up to a fifth of patients, this was achieved at surgery. [ABSTRACT FROM AUTHOR]

Abstract: Parry–Romberg syndrome (PRS) is a rare condition characterised by progressive hemi-facial atrophy. Here we present a PRS case with alien-hand syndrome, which has not previously been described in adult onset disease. On the basis of the presumed auto-immune pathology of PRS we justify the treatment strategy we successfully used in this patient. A review of the literature was extensively done for understanding the history of alien hand sign over the years. [Copyright &y& Elsevier]

Daratumumab is very efficacious in multiple myeloma. Few reports are present about efficacy in extramedullary myeloma. We report here daratumumab efficacy in extramedullary ocular myeloma in a young 46‐year‐old man diagnosed 3 years earlier and relapse refractory to five previous lines of therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Stroke warning syndrome (SWS) is a rare cause of stroke characterized by recurrent and short-lasting episodes of transient focal neurological deficits leading up to infarction. On the basis of clinical findings and neuroimaging, it can be capsular, pontine, or callosal. The aim of this study is to evaluate the prevalence of SWS in patients admitted to our Stroke Unit for an ischemic stroke and to look for the difference in outcome between patients treated or not with systemic thrombolysis by intravenous recombinant tissue plasminogen activator (IV-rtPA). Methods: Among the 967 patients admitted to our Stroke Unit between April 2008 and January 2013 for ischemic stroke, we identified 18 patients with SWS. Nine patients underwent IV-rtPA (IV Group) and the other 9 (No IV Group) other therapies. Results: The prevalence of SWS in our population was 1.8%. The most common risk factors were hypertension and dyslipidemia in both groups. A good outcome at 3-month follow-up (modified Rankin Scale 0–2) was found in 3 patients (33%) in IV Group and in 5 patients (55%) in No IV Group. Conclusion: SWS is an under-recognized syndrome. Intravenous rt-PA treatment seems to have lower efficacy than in other subtypes of strokes, but none of the patients with SWS undergoing treatment presented haemorrhagic transformation or other complications. [Copyright &y& Elsevier]

BACKGROUND: Intracranial involvement in multiple myeloma is extremely rare. The effect of new drugs (eg, thalidomide, bortezomib, lenalidomide) with respect to old drugs (eg, alkylators, steroids) has not been reported. METHODS: We collected clinical and biological data of patients presenting with an osteo-dural or primary dural multiple myeloma (OD-DMM) or a central nervous system myelomatosis (CNS-MM) by sending a questionnaire to the centers of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA). RESULTS: A total of 50 patients were registered. New therapies were used in 35 patients, whereas 15 patients received old treatments. Twenty-five out of 50 patients obtained a complete remission or a very good partial remission (CR+VGPR). Overall survival (OS) for CNS-MM was 6 months, for OD-DMM 25 months. OS was 25 months for patients treated with new agents versus 8 months with old agents. Improved OS and progression-free survival were predicted by response (CR+VGPR) and by patients who underwent stem cell transplantation versus chemotherapy. β2-Microglobulin >5 mmol/L was a poor prognostic factor. Multivariate analysis showed poor survival for patients with β2-microglobulin >5 mmol/L and better survival for patients achieving CR+VGPR. CONCLUSIONS: The overall data highlight the relevance of therapy with new drugs in intracranial myeloma, providing a framework for future clinical trials. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

The purpose of this case report is to describe MR imaging and CT findings of a patient in whom the first clinical and neuroradiological manifestation of a metastatic lung adenocarcinoma was unilateral trigeminal neuropathy caused by a presumed metastasis involving cisternal and Meckel's cave segments of ipsilateral trigeminal nerve. MR imaging and CT scan differential diagnosis of expansive lesions of the intracranial trigeminal nerve must include metastases. Physicians and neuroradiologists must be aware of metastases as an uncommon cause of trigeminal neuropathy, even as the presenting condition of cancer. [ABSTRACT FROM AUTHOR]

BSTRACT BACKGROUND AND PURPOSE [ABSTRACT FROM AUTHOR]

Perivascular, or Virchow–Robin, spaces of the brain represent interstitial fluid-filled spaces continuous with subpial spaces, and not invagination of cerebrospinal fluid-filled subarachnoid spaces. Regression of a dilated, or even giant, perivascular space occurs rarely. The purpose of this paper is to describe magnetic resonance imaging evidence of complete regression of dilated perivascular spaces (dPVSs). Patient 1 was a 76-year-old woman with right hemiparesis and aphasia from a left cranial vault meningioma infiltrating the superior sagittal sinus, and a left temporal lobe giant perivascular space. Patient 2 was a 70-year-old man with pituitary apoplexy, vasospasm, cerebral ischemia, and two dPVSs, one in the right temporal lobe, and one in the left anterior perforate substance. Patient 3 was a 78-year-old man with a generalized seizure, and a right temporal lobe dPVS. In all the patients, temporal lobe giant or dPVSs underwent regression, following meningioma subtotal resection (patient 1) or pituitary lesion shrinkage (patient 2), or spontaneously (patient 3). In patient 2, the left anterior perforate substance dPVS was unchanged. Temporal lobe giant or dPVSs may regress, eventually together with resection or regression of intracranial tumors, also distant from the PVSs. Cerebral edema does not seem the only factor influencing dilatation of PVSs. [ABSTRACT FROM AUTHOR]

The purpose of this pictorial essay is to increase awareness of the clinical presentation, neuroradiological findings, treatment options, and neuroradiological follow-up of plasmacytomas and multiple myeloma with intracranial growth. This pictorial essay reviews the clinical features and neuroradiological findings in seven patients (four women, three men; age range at diagnosis 62–82 years) followed in two institutions. Six patients, one with IgG-κ plasmacytoma, and five with IgG-κ ( n = 3), IgG-λ ( n = 1), and nonsecretory ( n = 1) multiple myeloma, had been seen over a period of 9 years in one institution, and the other patient with IgG-κ plasmacytoma had been seen over a period of 3.5 years in the other. Intracranial involvement is rare, most frequently resulting from osseous lesions in the cranial vault, skull base, nose, or paranasal sinuses. Primary dural or leptomeningeal involvement is rarer. Some typical findings of a dural and/or osseous plasmacytoma include iso- to hyperdensity on CT scan, T1 equal to high signal intensity and T2 markedly hypointense signal on MRI, and high vascularity possibly documented on intraarterial digital subtraction angiography. However, the neuroradiological findings generally lack specificity, since they are generally no different from those of meningioma, metastasis, lymphoma, dural sarcoma, plasma cell granuloma, infectious meningitis, and leptomeningeal carcinomatosis. The spectrum of clinical and neuroradiological evaluation shows that intracranial involvement from plasmacytoma and multiple myeloma must be taken into account in the differential diagnosis of cranial osseous and meningeal disease. [ABSTRACT FROM AUTHOR]

A newly described disease is characterized by anterior bilateral temporal lobe cysts associated with multilobar leukoencephalopathy and a non-progressive clinical course. We report a patient with bilateral anterior temporal lobe cystic changes associated with a non-progressive neurological disorder, microcephaly, spasticity, mental retardation, and sensorineural deafness. From the literature, 12 other patients have shown a similar phenotype. The common neuroradiological findings in these patients have been bilateral anterior temporal lobe cystic changes and non-progressive leukoencephalopathy. By contrast, variability in the clinical phenotype has been observed, ranging from severe neuromotor handicap with mental retardation and microcephaly to spasticity in the lower limbs associated with normal cognitive function. The pathological basis of the defect remains to be defined. [Copyright &y& Elsevier]

Simple Summary: Glioblastoma is a highly aggressive type of brain tumor that is very difficult to treat, and surgery is crucial for improving patient survival. However, there are significant differences in access to brain tumor surgery based on factors like income, location, and available healthcare resources. People in low- and middle-income countries often struggle to receive the surgery they need due to a lack of specialized doctors, inadequate healthcare facilities, and financial challenges. As a result, patients in these regions are often diagnosed later, receive less effective treatment, and have lower survival rates compared to those in wealthier countries. This not only affects the patients but also adds economic and social burdens to their communities. The study calls for urgent actions to address these inequalities through international cooperation, better healthcare policies, and fair distribution of resources, with the goal of improving access to brain tumor surgeries for everyone, no matter where they live. Glioblastoma: a highly aggressive brain tumor, presents substantial challenges in treatment and management, with surgical intervention playing a pivotal role in improving patient outcomes. Disparities in access to brain tumor surgery arise from a multitude of factors, including socioeconomic status, geographical location, and healthcare resource allocation. Low- and middle-income countries (LMICs) often face significant barriers to accessing surgical services, such as shortages of specialized neurosurgical expertise, limited healthcare infrastructure, and financial constraints. Consequently, glioblastoma patients in LMICs experience delays in diagnosis, suboptimal treatment, and poorer clinical outcomes compared to patients in high-income countries (HICs). The clinical impact of these disparities is profound. Patients in LMICs are more likely to be diagnosed at advanced disease stages, receive less effective treatment, and have lower survival rates than their counterparts in HICs. Additionally, disparities in access to surgical care exacerbate economic and societal burdens, emphasizing the urgent need for targeted interventions and health policy reforms to address healthcare inequities. This review highlights the importance of addressing global disparities in access to brain tumor surgery for glioblastoma through collaborative efforts, policy advocacy, and resource allocation, aiming to improve outcomes and promote equity in surgical care delivery for all glioblastoma patients worldwide. [ABSTRACT FROM AUTHOR]

Evidence of areas of increased attenuation density within lateral ventricles at computed tomography (CT) of the brain is a finding of acute or subacute intraventricular hemorrhage. The purpose of this case report is to describe a 14-year-old female who presented with an episode of complicated migraine. Brain CT showed an area of high attenuation density (35 Hounsfield Units) in the trigone and occipital horn of the right lateral ventricle, mimicking a blood-fluid level from subacute intraventricular hemorrhage. Magnetic resonance imaging (MRI) of the brain showed that this resulted from gray matter lining a deep calcarine fissure. A deep calcarine fissure may mimic intraventricular hemorrhage at CT. Correct CT and MRI interpretation allows to avoid invasive diagnostic tests including lumbar puncture or intra-arterial catheter angiography. [ABSTRACT FROM AUTHOR]

In a 33-year-old male patient with multiple sclerosis, brain magnetic resonance imaging incidentally showed a narrow right intracranial internal carotid artery. Gadolinium-enhanced magnetic resonance angiography showed absence of the right common carotid artery. Right external and internal carotid arteries arose separately from the ipsilateral innominate artery and subclavian artery, respectively. Color-Doppler ultrasound confirmed this finding. Embriologically, the case could be interpreted as the disappearance of the third aortic arch with persistence of the carotid duct connecting the third and fourth aortic arches. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which the central nervous system involvement with multiple myeloma has been discussed.

Purpose: To describe the neuroradiological features of intraocular medulloepithelioma.Methods: We retrospectively analyzed the clinical, histopathological, and MRI data of five children with medulloepithelioma. In addition to conventional images, DWI was performed in four patients and mean ADC was calculated; this was limited to the technique of this cohort of patients. DCE was performed in all patients. This is the first paper that presents diffusion and perfusion characteristics of medulloepithelioma.Results: Four tumors were malignant teratoid variants, two non-teratoid variants. Tumors were hyperintense on T1-weighted images and hypointense on T2-weighted images. Calcifications were detectable in two out of five tumors. Cavities were detectable in three out of five tumors. All tumors showed some degree of enhancement. The mean ADC of all four patients was 1.156 ± 242.75 × 10−3 mm2/s. Mean ktrans, Ve, Kep, TME, AUC, SER, and peak enhancement were 0.082 ± 0.054, 0.19 ± 0.076, 0.31 ± 0.084, 0.97 ± 0.0784, 1.22 ± 0.81, 67.34 ± 31.7, and 14.84 ± 7.34 respectively. TICs showed a very high ratio of slow increase, > 50% persistence and some degree of wash out. Teratoid variants showed higher K-trans, AUC, VE, TME, and persistent TIC pattern than non-teratoid ones, while plateau pattern ratio was lower.Conclusion: Conventional MR findings were similar to previously reported cases. Mean ADCs were moderately high. TICs showed slow increase and presence of wash out. K-trans, AUC, VE, and TME were higher in teratoid variants. Permeability parameters in differential diagnosis with lesions mimicking medulloepithelioma need further investigations. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 67-year-old woman with dizziness. Axial magnetic resonance images showed a right frontal mass that completely removed permitted to make IgG-k plasmacytoma diagnosis. The article discusses intracranial involvement in multiple myeloma (IC-MM) which is a rare extramedullary presentation or complication of MM.

Purpose: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare potentially reversible encephalopathy associated with an autoimmune process against proteins deposited in the walls of cortical and leptomeningeal brain vessels. Definite diagnosis requires histopathological features of vascular inflammation and amyloid deposition from brain biopsy. Clinical-neuroradiological criteria have been recently introduced and validated to reduce the need for biopsy. The purpose of this paper is to report a historical retrospective review of clinical-neuroradiological follow-up of two patients with probable CAA-ri and five patients with a reasonably probable suspect of CAA-ri (4 females, 3 males, patient's age at admission: 66–79 years) seen at our institution between 2007 and 2021, focusing on clinical and neuroradiological awareness to this entity and variable response to immunotherapy. Materials and methods: Clinical features at presentation included subacute to acute confusion (6/7), seizures (4/7), cognitive impairment (5/7), and focal neurological signs (3/7). Neuroradiology included braincomputed tomography followed by magnetic resonance imaging. Infectious diseases and autoimmune workups were then performed. Results: CSF analysis was performed in two patients. Cerebral angiography was performed in two patients, to rule out vascular malformations. Hemorrhagic posterior reversible encephalopathy syndrome has been suspected in two patients. Four patients underwent immunotherapy with corticosteroids followed by reduction of brain dysfunctions. Three patients did not undergo immunotherapy but underwent clinical and/or neuroradiological remission. Conclusions: Patients with CAA-ri present a rare steroid-responsive acute to subacute brain dysfunction. Thus, it has to be known and recognized both clinically and neuroradiologically. Spontaneous clinical and/or neuroradiological improvement is possible in patients with mild symptoms. [ABSTRACT FROM AUTHOR]

Despite the commonly observed association of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies with bilateral optic neuritis, their connection to uveitis is largely unexplored. The presented case involves a 41-year-old male with uveitis and bilateral optic neuritis, subsequently diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This case, characterized by bilateral optic neuritis associated to anti-MOG antibodies and the concurrent onset of unilateral anterior uveitis, provides further evidence concerning the features of intraocular inflammation in MOGAD. The patient’s treatment response, including the use of rituximab due to contraindications to oral steroids, emphasizes the importance of personalized management strategies in MOGAD-associated ocular manifestations. [ABSTRACT FROM AUTHOR]

Background and Purpose: Obstructive sleep apnea (OSA) syndrome is a sleep disorder characterized by excessive snoring, repetitive apneas, and nocturnal arousals, that leads to fragmented sleep and intermittent nocturnal hypoxemia. Morphometric and functional brain alterations in cortical and subcortical structures have been documented in these patients via magnetic resonance imaging (MRI), even if correlational data between the alterations in the brain and cognitive and clinical indexes are still not reported. Methods: We examined the impact of OSA on brain spontaneous activity by measuring the fractional amplitude of low‐frequency fluctuations (fALFF) in resting‐state functional MRI data of 20 drug‐naïve patients with OSA syndrome and 20 healthy controls matched for age, gender, and body mass index. Results: Patients showed a pattern of significantly abnormal subcortical functional activity as compared to controls, with increased activity selectively involving the thalami, specifically their intrinsic nuclei connected to somatosensory and motor‐premotor cortical regions. Using these nuclei as seed regions, the subsequent functional connectivity analysis highlighted an increase in patients' thalamocortical connectivity at rest. Additionally, the correlation between fALFF and polysomnographic data revealed a possible link between OSA severity and fALFF of regions belonging to the central autonomic network. Conclusions: Our results suggest a hyperactivation in thalamic diurnal activity in patients with OSA syndrome, which we interpret as a possible consequence of increased thalamocortical circuitry activation during nighttime due to repeated arousals. [ABSTRACT FROM AUTHOR]

Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to milder and later-onset gait disorders with central hypomyelination, with or without additional non-neurological signs. Recently, a milder phenotype consisting of late-onset spastic ataxia without hypomyelinating leukodystrophy has been suggested to be specific to the intronic c.1909 + 22G > A mutation in POLR3A. Here, we present 10 patients from 8 unrelated families with POLR3A-related late-onset spastic ataxia, all harboring the c.1909 + 22G > A variant. Most of them showed an ataxic-spastic picture, two a "pure" cerebellar phenotype, and one a "pure" spastic presentation. The non-neurological findings typically associated with POLR3A mutations were absent in all the patients. The main findings on brain MRI were bilateral hyperintensity along the superior cerebellar peduncles on FLAIR sequences, observed in most of the patients, and cerebellar and/or spinal cord atrophy, found in half of the patients. Only one patient exhibited central hypomyelination. The POLR3A mutations present in this cohort were the c.1909 + 22G > A splice site variant found in compound heterozygosity with six additional variants (three missense, two nonsense, one splice) and, in one patient, with a novel large deletion involving exons 14–18. Interestingly, this patient had the most "complex" presentation among those observed in our cohort; it included some neurological and non-neurological features, such as seizures, neurosensory deafness, and lipomas, that have not previously been reported in association with late-onset POLR3A-related disorders, and therefore further expand the phenotype. [ABSTRACT FROM AUTHOR]

Choreoathetosis is a rare neurologic complication of the diabetic disease. The purpose of this case report is to increase the knowledge of such occurrence by describing the case of an elderly woman who was admitted to our institution for an over 20-day history of choreic movement in the left side of the body. She had a 6-year history of type 2 diabetes mellitus with a poor metabolic control including a glycosylated hemoglobin of 13%. Unenhanced computed tomography of the brain was negative. At magnetic resonance imaging, the right putamen showed high signal intensity on T1-weighted images and an area of high signal intensity on T2-weighted images, diffusion-weighted images and apparent diffusion coefficient maps. During the hospitalization, an adequate diet therapy was performed, and insulin therapy was gradually adjusted using regular insulin at main meals associated with basal insulin (glargine) 'bed time'. This resulted in progressive normalization of blood glucose values and an improvement of dyskinesia. There is a deep correlation between non-chetotic hyperglycemia and neurologic lesions leading to choreoathetosis. The etiopathogenesis seems multifactorial, and include hyperosmolar damage on cortical cells, alteration in GABA neurotransmission and in cerebral vascular self-regulation mechanism. Notably, in DM type 2 choreoathetosis may be related to both vascular and neuro-metabolic alterations in the basal nucleus due to inadequate glycemic control continuing in the time. This rare complication of DM type 2 is a pathological entity to be considered benign, since it is generally transient and reversible with the attainment of an adequate metabolic compensation. [ABSTRACT FROM AUTHOR]

Spondylolysis is an osseous defect of the pars interarticularis, thought to be a developmental or acquired stress fracture secondary to chronic low-grade trauma. It is encountered most frequently in adolescents, most commonly involving the lower lumbar spine, with particularly high prevalence among athletes involved in certain sports or activities. Spondylolysis can be asymptomatic or can be a cause of spine instability, back pain, and radiculopathy. The biomechanics and pathophysiology of spondylolysis are complex and debated. Imaging is utilized to detect spondylolysis, distinguish acute and active lesions from chronic inactive non-union, help establish prognosis, guide treatment, and to assess bony healing. Radiography with satisfactory technical quality can often demonstrate a pars defect. Multislice CT with multiplanar reformats is the most accurate modality for detecting the bony defect and may also be used for assessment of osseous healing; however, as with radiographs, it is not sensitive for detection of the early edematous stress response without a fracture line and exposes the patient to ionizing radiation. Magnetic resonance (MR) imaging should be used as the primary investigation for adolescents with back pain and suspected stress reactions of the lumbar pars interarticularis. Several imaging pitfalls render MR imaging less sensitive than CT for directly visualizing the pars defects (regional degenerative changes and sclerosis). Nevertheless, the presence of bone marrow edema on fluid-sensitive images is an important early finding that may suggest stress response without a visible fracture line. Moreover, MR is the imaging modality of choice for identifying associated nerve root compression. Single-photon emission computed tomography (SPECT) use is limited by a high rate of false-positive and false-negative results and by considerable ionizing radiation exposure. In this article, we provide a review of the current concepts regarding spondylolysis, its epidemiology, pathogenesis, and general treatment guidelines, as well as a detailed review and discussion of the imaging principles for the diagnosis and follow-up of this condition. [ABSTRACT FROM AUTHOR]

This study describes a patient with lateral medullary ischemia (LMI) presenting with persistent hiccups followed by vertigo with horizontal head-shaking-induced contralesional nystagmus (HSN) and discusses pertinent pathophysiology. A 65-year-old man presented with persistent hiccups and disabling spells of vertigo, lasting 30 seconds that became much more frequent and associated with lateropulsion to the right. A strong left beating HSN was evident. Magnetic resonance imaging and angiography, and intra-arterial cerebral digital subtracted angiography showed subacute ischemic lesions in the right lateral medulla and ipsilateral inferior cerebellar hemisphere, and two tight stenoses of the V1 and V4 segments of the right vertebral artery. Patient was treated by intravenous heparin and oral clopidogrel. After 48 hours, hiccups disappeared. One month later, vertigo spells were less frequent but still disabling. Endovascular stenting of the right vertebral artery stenoses was then performed. In the subsequent four years, the patient had no further episodes of hiccups or vertigo. Less intense HSN persisted. Hiccups followed by vertigo, lateropulsion, and HSN had been the clinical presentation of LMI and cerebellar ischemia, without other major neurologic or ocular motor findings. This unusual clinical variant of LMI could mimic a more benign labyrinthine lesion, and possibly leading to a dangerously delayed treatment. [ABSTRACT FROM AUTHOR]

Our pilot study aimed to investigate the efficacy and tolerability of intra-articular (i.a.) injections of infliximab as a therapy for erosive osteoarthritis of the hands. Ten women with bilateral involvement of the hands and typical erosive osteoarthritis radiographic findings were enrolled and followed for 12 months. All the patients were refractory to conventional drugs. Treatment consisted in monthly i.a. injections of 0.2 ml of infliximab (0.1 mg/ml) in each affected proximal and distal interphalangeal joint of the most involved hand, identified on the basis of clinical and radiological examinations. The other hand was treated with physiological saline (control). The patients did not know which hand was receiving infliximab. Clinical response was evaluated at enrollment, after 6 and 12 months. Posteroanterior radiographs of both hands were obtained at baseline and 12 months later. At 6 months all the patients experienced relief from spontaneous pain and pain on lateral pressure in the hand treated with infliximab and these findings became statistically significant after 1 year. No important modifications were recognized in the hand treated with physiological saline. The anatomical lesion progression system radiological score indicated a reduction, even if not statistically significant, in the hand treated with infliximab and a tendency to slow worsening in the hand treated with physiological saline at 12-month follow-up. No local or systemic adverse reactions were recorded. Our study shows the symptomatic effect and a possible disease modifying action of i.a. infliximab in erosive osteoarthritis of the hands. [ABSTRACT FROM AUTHOR]

Abstract: It is known that the intramuscular injection of human chorionic gonadotropin (hCG) lowers the threshold for motor evoked responses (MEPs) in the first dorsal interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) in humans. We describe the case of a patient with a clinically silent left-sided nasofrontal dermoid cyst who, while being treated with hCG/LH for hypogonadotropic hypogonadism, presented with simple partial seizures, ipsilateral to the cyst, with secondary generalization. Motor cortex excitability was studied by single and paired TMS and MEPs were recorded from FDI. Resting motor threshold (RMT), active motor threshold (AMT), MEP size, intracortical inhibition (ICI) and intracortical facilitation (ICF) were tested during and after suspension of hormonal therapy. RMT and AMT were lower, MEP size was larger, ICI was decreased while ICF was slightly diminished during treatment. Overall, this indicated a reduced intracortical inhibition during hormonal therapy. It is concluded that treatment with hCG/LH may favour seizure onset in the presence of potentially epileptogenic lesions such as an intracranial dermoid cyst. [Copyright &y& Elsevier]

Abstract: The authors report the clinical, neuroimaging, muscle biopsy and mtDNA findings in a patient affected by bilateral hearing loss and mental retardation since infancy, presenting at age 31 years with a rapid deterioration of mental status and ataxia leading to vegetative condition and death at the age of 32 years. Clinical and genetic studies have been also performed in the mother, affected by neurosensorial hearing loss. Muscle biopsy showed severe mitochondrial alterations in the propositus and evidence of mitochondrial alterations in his mother. Direct mtDNA sequencing in all family members revealed the known 7472insC mutation and the recently described A7472C sequence variation in the tRNASer(UCN)gene. RFLP–PCR confirmed the heteroplasmic nature of the two mutations and failed to find the second transversion in 200 controls. The percentage of mutant genomes harbouring 7472insC ranged from 3 to 7% in asymptomatic family members to 70% in the proband and his mother, whereas the percentage of A7472C mutant genomes was about 90% in all maternal relatives except the proband (56%) and his sister (5%). In conclusion, this is the first report of a rapidly progressive encephalopathy in association with the 7472insC mutation in mtDNA, combined with an A>C variation at the same nucleotide with a possible suppression effect on the pathogenic mutation. [Copyright &y& Elsevier]

Background:. Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare, poorly understood, inflammatory disease, usually involving the dura mater of skull base, tentorium, and falx, and presenting with headache, progressive cranial nerve palsies, and cerebellar dysfunction. Patients and Methods:. In four patients, the diagnosis of IHCP has been made on the basis of extensive clinical, and radiological investigation, and confirmed by dural biopsy in three patients. The clinical follow-up ranges from 24 to 120 months. Results :. At diagnosis, all the patients complained of severe, progressively increasing headache, two had simple or complex partial seizures, but none had cranial nerve palsies. Two patients had electrophysiological evidence of axonal peripheral neuropathy, biopsy-proved in one of them. In all the patients, MRI showed linear or focal thickening of the dura mater of the tentorium and/or of the convexity, sparing the skull base. In one patient, MRI findings resembled chronic subdural hematoma. Dural biopsy demonstrated fibrosis and prominent CD4+ T-cells inflammatory infiltrate. Pachymeningitis was highly responsive to steroid therapy, as was the peripheral neuropathy. In three patients, temporary steroids withdrawal led to dramatic clinical worsening including status epilepticus in one. Conclusions :. In the patients here reported, absence of cranial nerve impairment, seizures, MRI findings resembling chronic subdural hematoma, and association with polineuropathy were unusual findings of IHCP. Moreover, the type of inflammatory infiltrate, lacking in previous reported cases, suggests a probable pathogenetic role for cell-mediated immunity of unknown origin. [ABSTRACT FROM AUTHOR]

Interestingly, patient 2 also had Crohn's disease, albeit not in active phase as demonstrated by instrumental investigations and blood test, thereby excluding Crohn's disease as possible cause of patient's symptoms. Computed tomography (CT) may be uninformative and magnetic resonance imaging (MRI) is necessary. CT may show cerebellar swelling and low density of the areas of the cerebellum involved, but these findings may be too subtle to identify, as in our patient 2. Typical MRI findings, if any, strongly support a diagnosis of acute cerebellitis in patients with compatible clinical presentation and cerebrospinal fluid (CSF) findings. [Extracted from the article]

Background and purpose: Adult brainstem gliomas are rare primary brain tumours with heterogeneous clinical course. The low frequency of these tumours makes it difficult to achieve high-quality evidence regarding prognostic factors, adequate therapeutic approach and outcome in such patients. Methods: In this retrospective study, we analysed clinical, radiological, molecular, prognostic and therapeutic factors in a series of 47 histologically proven adult brainstem gliomas recruited over a 20-year period (1998–2018). Results: Twenty-two patients were male, 25 female with median age of 39 years. The tumour involved one brainstem segment in 20 cases and 2 or more segments in 27. Contrast enhancement was reported in 28 cases. Surgical procedures included biopsy in 26 cases and partial/total resection in the remaining 21. Histological diagnosis was of low-grade glioma in 23 patients, high-grade glioma in 22 and non-diagnostic in 2 cases. Data regarding molecular biology were available for 22 patients. Median overall survival was 35 months, in particular 16 months in high-grade glioma and 84 months in low-grade glioma. At univariate analysis, tumour grade was the only factor with a statistically significant impact on survival time (p = 0,003), whereas younger age, better performance status and total/subtotal resection showed a trend to more prolonged survival. This study also confirms safety of biopsy/surgery in adult brainstem glioma patients and shows a clear trend to a more frequent assessment of molecular biology data. Conclusions: Further prospective multicentre efforts, and hopefully clinical trials, are necessary to improve outcome in this neglected glioma patient population. [ABSTRACT FROM AUTHOR]

A 71 year old female with multiple myeloma presented with back pain seven year after autologous stem cell transplant. Skeletal bone survey and magnetic resonance imaging did not show a relapse that was evidenced by CT/PET. Lenalidomide as single agent induced a complete disappearance of the lesions 6 months later and confirmed after one year at CT/PET. [ABSTRACT FROM AUTHOR]

Purpose: Teleconsultation is a consultation between two or more physicians about the diagnostic work-up and therapeutic strategy in the treatment of an individual case by means of modern telematics. 'Drip-and-ship' teleconsultation model consists of the transfer of patients, through telematics stroke networks, with large arteries occlusions from primary to comprehensive stroke centers equipped for endovascular therapy. We retrospectively investigated appropriateness, safety, and effectiveness of 'drip-and-ship' teleconsultation model in a rural area of Tuscany.Methods: Outcome measures were: door-to-ship time (including door-to-needle time), ratio of number treated/total sent patients, adverse events/mortality during transfer, and mortality and modified Rankin scale at 90 days. Analysis of non-treated patients was also done.Results: Seventy-eight patients were included; 16/78 patients were sent for endovascular therapy alone, and 62/78 for "drip-and-ship"; 12 patients were not treated. Door-to-ship, and door-to-needle times (mean ± SD) were 105 ± 29.8 and 62.5 ± 37.5 min, respectively. The ratio number of treated/total sent patients was 0.85. At 90 days, the global mortality rate was 21%, and 40% of patients showed favorable outcome. The main cause of non-treatment was spontaneous recanalization.Conclusions: The high value for treated/total sent patients' ratio underlines that "drip-and-ship" teleconsultation model is appropriate and effective, with a few untreated patients. The model is safe, without adverse events during transfer. Taken together, our outcomes are in line with the previous reports. "Drip-and-ship" teleconsultation model is safe and effective in rural areas, allowing good selections and rapid treatments for stroke patients, based on the transfer from the primary to the comprehensive stroke center. [ABSTRACT FROM AUTHOR]

Ring-shaped lateral ventricular nodules (RSLVNs) are commonly considered as benign asymptomatic lesions, which are sporadically detected as incidental findings on routine brain magnetic resonance imaging scans. Despite their not irrelevant frequency, the exact biological nature of these lesions remains largely unknown due to the lack of histopathologic studies. Here we present the clinical, neuroradiologic, and histopathologic findings of an unusual case of symptomatic multiple RSLVNs. A 44-year-old otherwise healthy man presented with a recent history of headache and retching. Neuroradiologic imaging revealed the presence of multiple RSLVNs, the largest of which, located in the cella media of the right lateral ventricle, exerted a mild to moderate mass effect on adjacent brain parenchyma. This latter nodule was successfully removed, with complete resolution of the symptoms. Histopathology revealed glial differentiation, and the specimen was diagnosed as subependymoma. This report provides novel evidence characterizing RSLVNs as possible variants of subependymoma with a peculiar imaging appearance, also suggesting that, like subependymomas, they may occasionally grow large enough to cause mass effect−related symptoms, thus requiring neurosurgical intervention. [ABSTRACT FROM AUTHOR]

Until very few years ago, the oncology community dogmatically excluded any clinical potential for immunotherapy in controlling brain metastases. Therefore, despite the significant therapeutic efficacy of monoclonal antibodies to immune check-point(s) across a wide range of tumor types, patients with brain disease were invariably excluded from clinical trials with these agents. Recent insights on the immune landscape of the central nervous system, as well as of the brain tumor microenvironment, are shedding light on the immune-biology of brain metastases. Interestingly, retrospective analyses, case series, and initial prospective clinical trials have recently investigated the role of different immune check-point inhibitors in brain metastases, reporting a significant clinical activity also in this subset of patients. These findings, and their swift translation in the daily practice, are driving fundamental changes in the clinical management of patients with brain metastases, and raise important neuroradiologic challenges. Along this line, neuro-oncology undoubtedly represents an additional area of active investigation and of growing interest to support medical oncologists in the evaluation of clinical responses of brain metastases to ICI treatment, and in the management of neurologic immune-related adverse events. Aim of this review is to summarize the most recent findings on brain metastases immunobiology, on the evolving scenario of clinical efficacy of ICI therapy in patients with brain metastases, as well as on the increasing relevance of neuroradiology in this therapeutic setting. [ABSTRACT FROM AUTHOR]

Highlights • Percutaneous transluminal angioplasty (PTA) had been under scrutiny as multiple sclerosis treatment. • We prospectively quantified eventual neurophysiological and urodynamic changes occurring post PTA. • Central neural conduction properties remained overall unchanged despite transient subjective well-being improvement. Abstract Objective Verify whether Percutaneous Transluminal Angioplasty (PTA) may affect neural conduction properties in Multiple Sclerosis (MS) patients, thereby modifying patients' disability, with prospective neurophysiological, urodynamic, clinical and subjective well-being evaluations. Methods In 55 out of 72 consecutively screened MS patients, the following procedures were carried out before (T0), at 2–6 months (T1) and at 6–15 months (T2) after a diagnostic phlebography, eventually followed by the PTA intervention if chronic cerebrospinal venous insufficiency (CCSVI) was diagnosed: clinical/objective evaluation (Expanded Disability Status Scale, EDSS), ratings of subjective well-being, evaluation of urodynamic functions and multimodal EPs (visual, acoustic, upper and lower limbs somatosensory and motor evoked potentials). Results The number of dropouts was relatively high, and a complete set of neurophysiological and clinical data remained available for 37 patients (19 for urological investigations). The subjective well-being score significantly increased at T1 and returned close to basal values at T2, but their degree of objective disability did not change. Nevertheless, global EP-scores (indexing the impairment in conductivity of central pathways in multiple functional domains) significantly increased from T0 (7.9 ± 6.0) to T1 (9.2 ± 6.3) and from T0 to T2 (9.8 ± 6.3), but not from T1 and T2 (p > 0.05). Neurogenic urological lower tract dysfunctions slightly increased throughout the study. Conclusions The PTA intervention did not induce significant changes in disability in the present cohort of MS patients, in line with recent evidence of clinical inefficacy of this procedure. Significance Absence of multimodal neurophysiological and functional testing changes in the first 15 months following PTA suggests that conduction properties of neural pathways are unaffected by PTA. Current findings suggest that the short-lived (2–6 months), post-PTA, beneficial effect on subjective well-being measures experienced by MS patients is likely related to a placebo effect. [ABSTRACT FROM AUTHOR]

Purpose. To compare the therapeutic results of two radiotherapy (RT) dose schedules in combined temozolomide- (TMZ-) RT treatment in newly diagnosed glioblastoma (GB), according to the O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status. Material and Method. Patients received either standard (60 Gy) or moderately escalated dose (70 Gy) radiotherapy (RT) with concomitant and adjuvant TMZ between June 2006 and October 2013. We retrospectively evaluated the therapeutic effectiveness of RT schedules in terms of Overall Survival (OS) and Progression-Disease Free Survival (PDFS) analyzing the MGMT methylation status. Results. One hundred and seventeen patients were selected for the present analysis. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the escalated schedule (HDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in unmethylated-MGMT GB patients, HDRT-TMZ and SDRT-TMZ groups had different median OS (p=0,01) and PDFS (p=0,007), that is, 8 months and 5 months for the SDRT-TMZ group and 14 months and 9 months for the HDRT-TMZ group, respectively. No difference in survival outcomes was found in methylated MGMT patients according to the two RT schedules (p=0,12). Conclusions. In our experience, unmethylated-MGMT GB patients benefited from a moderately escalated dose of RT plus TMZ. [ABSTRACT FROM AUTHOR]

Aims Cerebral small vessel disease ( SVD) is the leading cause of vascular dementia. Although the most of cases are sporadic, familial monogenic causes have been identified in a growing minority of patients. CADASIL, due to mutations of NOTCH3 gene, is the most common genetic SVD, and CARASIL, linked to HTRA1 gene mutations, is a rare but well known autosomal recessive SVD. Recently, also heterozygous HTRA1 mutations have been described in patients with familial SVD. To detect a genetic cause of familial SVD, we performed mutational analysis of HTRA1 gene in a large cohort of Italian NOTCH3-negative patients. Methods We recruited 142 NOTCH3-negative patients and 160 healthy age-matched controls. Additional control data were obtained from five pathogenicity prediction software. Results Five different HTRA1 heterozygous mutations were detected in nine patients from five unrelated families. Clinical phenotype was typical of SVD, and the onset was presenile. Brain magnetic resonance imaging ( MRI) showed a subcortical leukoencephalopathy, with involvement of the external and internal capsule, corpus callosum, and multiple lacunar infarcts. Cerebral microbleeds were also seen, while anterior temporal lobes involvement was not present. Conclusion Our observation further supports the pathogenic role of the heterozygous HTRA1 mutations in familial SVD. [ABSTRACT FROM AUTHOR]

Radiosurgery (SRS) is widely used in the treatment of brain oligo-metastases from NSCLC. The aim of present study is to evaluate the extent of perilesional edema in brain metastases as predictive factor of treatment response. This single center retrospective study included 42 consecutive patients (January 2011-December 2014) with 1-2 brain metastasis from NSCLC treated with Radiosurgery (SRS). Extent of perilesional edema was measured as maximal extension from the edge of lesion and classified as minor (<10 mm) or major (≥10 mm). We analyzed Modality of Brain Recurrence (MBR), classified as in-field or out-of- field, and Brain Progression Free-Survival (BPFS) after treatment stratified according to extent of perilesional edema. Analyzing modality of brain recurrence and BPFS, after a median follow-up of 6 months, we found that patients with minor edema had a better radiological response to SRS with none in-field recurrences and a lower risk of the onset of new brain lesions (out-of-field recurrence). Instead, patients group with major edema had a worse response rate of lesions treated, further, a higher risk of out-of-field brain relapse. Extent of perilesional edema in brain metastasis from NSCLC could be a predictive factor of response and brain progression after SRS treatment alone. [ABSTRACT FROM AUTHOR]

Several single gene disorders can potentially be overlooked in the differential diagnostic evaluation of patients with multiple sclerosis (MS). Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders associated with defective myelination of the central nervous system and mutations in PLP1 . Neurological symptoms are occasionally observed in female carriers of these mutations. Two women – the proposita (Pt1) and her mother (Pt2) – reported walking difficulties since adolescence and showed progressive cognitive decline. Their neurological examinations revealed spastic gait, pyramidal tract involvement and distal muscle atrophy in the legs. Peripheral neuropathy and diffuse white matter (WM) changes on brain MRI were also observed. Both patients had a preliminary diagnosis of primary progressive MS. Using a targeted method in next generation sequencing, the novel heterozygous c.210T > G/p.Y70* in PLP1 was identified in Pt2. The same mutation was also found in Pt1 but not in five healthy relatives. The mutation showed moderate-to-severe skewed X inactivation in tissues, and Western blotting revealed a significant reduction of PLP1 and DM20 in the sural nerve of Pt2. In conclusion a mother and daughter presented an X-linked dominant disorder with skewed X inactivation. The authors suggest that PLP1 testing might be considered in the evaluation of women with spastic paraparesis, cognitive decline and WM changes. [ABSTRACT FROM AUTHOR]

Background Complex I deficiency is the most common energy generation disorder which may clinically present at any age with a wide spectrum of symptoms and signs. The T10158C mutation ND3 gene is rare and occurs in patients showing an early rapid neurological deterioration invariably leading to death after a few months. Case presentation We report a 9 year-old boy with a mtDNA T10158C mutation showing a mild MELAS-like phenotype and brain MRI features congruent with both MELAS and Leigh syndrome. Epilepsia partialis continua also occurred in the clinical course and related to a mild cortical atrophy of the left perisylvian area. Discussion The present case confirms that the clinical spectrum of Complex I deficiency related to T10158C mutation ND3 gene is wider than previously described. Our observation further suggests that testing mutation in the MT-ND3 gene should be included in the diagnostic work-up of patients presenting with epilepsia partialis continua accompanied by suspicion of mitochondrial disorder. [ABSTRACT FROM AUTHOR]

Marchiafava-Bignami Disease (MBD) is a toxic demyelinating disease often diagnosed in chronic alcoholics. The disease process typically involves the corpus callosum and clinically presents with various manifestations resulting in MBD type A and type B on the basis of clinical condition, extent of callosal involvement and extracallosal involvement at brain magnetic resonance imaging (MRI), and prognosis. The death rate is high. We report a patient affected by MBD type B, who presented an isolated reversible splenial lesion at brain MRI and achieved a favorable recovery. [ABSTRACT FROM AUTHOR]

Introduction: Differentiation between normal solid (non-cystic) pineal glands and pineal pathologies on brain MRI is difficult. The aim of this study was to assess the size of the solid pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. Methods: We retrospectively analyzed the size (width, height, planimetric area) of solid pineal glands in 184 non-retinoblastoma patients (73 female, 111 male) aged 0-5 years on MRI. The effect of age and gender on gland size was evaluated. Linear regression analysis was performed to analyze the relation between size and age. Ninety-nine percent prediction intervals around the mean were added to construct a normal size range per age, with the upper bound of the predictive interval as the parameter of interest as a cutoff for normalcy. Results: There was no significant interaction of gender and age for all the three pineal gland parameters (width, height, and area). Linear regression analysis gave 99 % upper prediction bounds of 7.9, 4.8, and 25.4 mm, respectively, for width, height, and area. The slopes (size increase per month) of each parameter were 0.046, 0.023, and 0.202, respectively. Ninety-three percent (95 % CI 66-100 %) of asymptomatic solid pineoblastomas were larger in size than the 99 % upper bound. Conclusion: This study establishes norms for solid pineal gland size in non-retinoblastoma children aged 0-5 years. Knowledge of the size of the normal pineal gland is helpful for detection of pineal gland abnormalities, particularly pineoblastoma. [ABSTRACT FROM AUTHOR]

The toxicity risk of hyperhomocysteinemia is prevented through thiol drug administration which reduces plasma total homocysteine (tHcy) concentrations by activating thiol exchange reactions. Assuming that cysteine (Cys) is a homocysteinemia regulator, the hypothesis was verified in healthy and pathological individuals after the methionine loading test (MLT). The plasma variations of redox species of Cys, Hcy, cysteinylglycine, glutathione and albumin (reduced, HS-ALB, and at mixed disulfide, XSS-ALB) were compared in patients with cerebral small vessels disease (CSVD) ( n = 11), multiple sclerosis (MS) ( n = 12) and healthy controls ( n = 11) at 2-4-6 h after MLT. In MLT-treated subjects, the activation of thiol exchange reactions provoked significant changes over time in redox species concentrations of Cys, Hcy, and albumin. Significant differences between controls and pathological groups were also observed. In non-methionine-treated subjects, total Cys concentrations, tHcy and thiol-protein mixed disulfides (CSS-ALB, HSS-ALB) of CSVD patients were higher than controls. After MLT, all groups displayed significant cystine (CSSC) increases and CSS-ALB decreases, that in pathological groups were significantly higher than controls. These data would confirm the Cys regulatory role on the homocysteinemia; they also explain that the Cys-Hcy mixed disulfide excretion is an important point of hyperhomocysteinemia control. Moreover, in all groups after MLT, significant increases in albumin concentrations, named total albumin (tALB) and measured as sum of HS-ALB (spectrophometric), and XSS-ALB (assayed at HPLC) were observed. tALB increases, more pronounced in healthy than in the pathological subjects, could indicate alterations of albumin equilibria between plasma and other extracellular spaces, whose toxicological consequences deserve further studies. [ABSTRACT FROM AUTHOR]

Dysregulated EGFR in glioblastoma may inactivate the key autophagy protein Beclin1. Each of high EGFR and low Beclin1 protein expression, independently, has been associated with tumor progression and poor prognosis. High (H) compared to low (L) expression of EGFR and Beclin1 is here correlated with main clinical data in 117 patients after chemo- and radiotherapy. H-EGFR correlated with low Karnofsky performance and worse neurological performance status, higher incidence of synchronous multifocality, poor radiological evidence of response, shorter progression disease-free (PDFS), and overall survival (OS). H-Beclin1 cases showed better Karnofsky performance status, higher incidence of objective response, longer PDFS, and OS. A mutual strengthening effect emerges in correlative power of stratified L-EGFR and H-Beclin1 expression with incidence of radiological response after treatment, unifocal disease, and better prognosis, thus identifying an even longer OS group (30 months median OS compared to 18 months in L-EGFR, 15 months in H-Beclin1, and 11 months in all GBs) (P=0.0001). Combined L-EGFR + H-Beclin1 expression may represent a biomarker in identifying relatively favorable clinical presentations and prognosis, thus envisaging possible EGFR/Beclin1-targeted therapies. [ABSTRACT FROM AUTHOR]

We report a successfully treated case of spondylodiscitis and bloodstream infection due to vancomycin heteroresistant Staphylococcus capitis , in an adult immunocompetent patient with multiple antibiotics intolerance. S. capitis is rarely involved in osteomyelitis and, to our knowledge, this is the first report of vancomycin heteroresistance phenomenon in an S. capitis strain causing spondylodiscitis. [ABSTRACT FROM AUTHOR]

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant disorder characterized by white matter neurodegeneration, progressive cognitive decline, and motor symptoms. Histologically, it is characterized by axonal swellings ('spheroids'). To date, over 20 different mutations affecting the tyrosine kinase domain of the protein have been identified in the colony stimulating factor 1 receptor ( CSF1R) gene. Our goal is to describe three unrelated Italian patients affected by HDLS and carrying new CSF1R mutations, thus expanding the mutational spectrum and phenotypic presentation. CSF1R gene analysis was performed in 15 patients (age range 25-83 years) with undefined leukoencephalopathy and progressive cognitive decline. In three patients (two males and one female, aged 58, 37, and 48 years, respectively), new heterozygous missense mutations affecting the protein tyrosine kinase domain of the CSF1R gene were detected. In all of these patients, behavioural and cognitive changes were preceded by an ischemic stroke-like episode. A positive family history was present in only one case. [ABSTRACT FROM AUTHOR]