Neuroradiological Presentation Research Articles

Determinants of outcome of transsphenoidal surgery for Cushing disease in a single-centre series.

First-line therapy of Cushing disease (CD) is transsphenoidal surgery (TSS) aimed to obtain a complete removal of the pituitary adenoma and remission of disease. To analyse the surgical outcome of patients with CD who underwent TSS in our Centre. Retrospective analysis on patients with CD who underwent TSS between 1990 and 2016. We analysed 102 TSS that included: 84 first TSS and 18 second and third TSS. The overall remission rate after surgery was 76.5%, with a significant higher percentage of remitted patients after the first TSS compared to the subsequent TSS (82% vs 50%, p = 0.014). The remission after the first TSS was significantly higher when performed by a dedicated surgical team (DST) (89.8% vs 71% p = 0.04) and when the immunohistochemical examination confirmed the adrenocorticotropic adenoma (87% vs 55%, p = 0.04). Neuroradiological findings influenced the surgical outcome in a non-significant manner. Post-TSS complications were reported in 32 patients, with no significant variation when TSS was performed by DST. In case of reintervention, remission of disease was obtained in 72.7% of microadenoma, while no remitted patients were observed in case of macroadenomas. The DST did not significantly improve the outcome. Cushing disease is characterized by a broad spectrum of neuroradiological presentation. Despite the availability of a DST make the TSS a safe and effective first-line treatment among all these patients, a precise pre-treatment evaluation is needed in order to define the aim of neurosurgery and to schedule the management of recurrent disease.

An audit of cerebral venous thrombosis associated with pregnancy and puerperium in teaching hospital in North Eastern India.

Background and Purpose:Cerebral venous thrombosis (CVT) is characterized by its clinical pleomorphism and pathogenetic variability. We studied 87 patients with CVT associated with pregnancy, and puerperium to find clinical profile, neuroradiological presentation and prognosis.Methods:A retrospective analysis was conducted based on clinical records at our institute between June 2008 and June 2018 without any personally identifying information. The diagnosis of CVT was confirmed by magnetic resonance imaging, angiography, or neuropathological study.Results:Among 87 patients, there were 82 of CVT associated with puerperium and 5 during pregnancy. Fifty-five women were multiparous. Cesarean delivery, hypertension, and anemia were strongly and significantly associated with CVT. Final outcome was considered good with anticoagulation; mortality rate was 10.34%.Conclusion:CVT associated with pregnancy, and puerperium is not an uncommon entity and has acute onset and a better prognosis. Pregnancy-related hypertension and Cesarean delivery and anemia are important risk factors for CVT. Further studies are needed to evaluate the need for therapeutic strategies for patients with CVT during pregnancy and puerperium.

Central Nervous System Tuberculosis : Etiology, Clinical Manifestations and Neuroradiological Features.

As aresult of multilateral migration and globalization in times of humanitarian crises, western countries face apossible increase in the incidence of central nervous system tuberculosis (CNS TB). The diagnosis of CNS TB is challenging and often delayed due to the manifold and often non-specific presentation of the disease. The aim of this review is to analyze and summarize imaging features and correlated clinical findings of CNS TB. The different manifestations of CNS TB are explained and illustrated by characteristic neuroradiological as well as neuropathological findings. Anoverview on diagnostic and therapeutic approaches is provided. For clarity, tables summarizing the lesion patterns, differential diagnoses and diagnostic hints are added. The CNS TB can be manifested (1)diffuse as tuberculous meningitis (TBM), (2)localized as tuberculoma or (3)tuberculous abscess or (4)in extradural and intradural spinal infections. Information on clinical presentation, underlying pathology and the distinguishing features is demonstrated. The TBM is further described, which may lead to cranial nerve palsy, hydrocephalus and infarction due to associated arteritis of the basal perforators. The differential diagnoses are vast and include other infections, such as bacterial, viral or fungal meningoencephalitis, malignant causes or systemic inflammation with CNS. Complicating factors of diagnosis and treatment are HIV coinfection, multi-drug resistance and TB-associated immune reconstitution inflammatory syndrome (IRIS). Neurologists and (neuro-)radiologists should be familiar with the neuroradiological presentation and the clinical course of CNS TB to ensure timely diagnosis and treatment.

The Diagnosis and Treatment of Primary CNS Lymphoma.

Primary central nervous system lymphoma is a diffuse large B-celllymphoma with exclusive manifestation in the central nervous system (CNS), leptomeninges, and eyes. Its incidence is 0.5 per 100 000 persons per year.Currently, no evidence-based standard of care exists. This review is based on pertinent publications (2000-2017) retrieved by aselective search in PubMed. The clinical and neuroradiological presentation of primary CNS lymphoma isoften nonspecific, and histopathological confirmation is obligatory. The disease, if left un- treated, leads to death within weeks or months. If the patient's general condition permits, treatment should consist of a high-dose chemotherapy based on methotrexate (HD- MTX) combined with rituximab and other cytostatic drugs that penetrate the blood-brain barrier. Long-term survival can be achieved in patients under age 70 by adding non- myeloablative consolidation chemotherapy or high-dose chemotherapy with autologous stem cell transplantation (HD-AST) to the induction therapy. Clinical trials comparing the efficacy and toxicity of these two treatment strategies are currently underway. Con- solidation whole-brain radiotherapy is associated with the risk of severe neurotoxicity and should be reserved for patients who do not qualify for systemic treatment. Some 30% of patients are refractory to primary treatment, and at least 50% relapse. In patients who are still in good general condition, relapse can be managed with HD-AST. Re- exposure to conventional HD-MTX-based polychemotherapy is another option, if the initial response was durable. The 5-year survival rate of all treated patients is 31%,according to registry data. Current recommendations for the treatment of primary CNS lymphomaare based on only a small number of prospective clinical trials. Patients with this disease should be treated by interdisciplinary teams in experienced centers, andpreferably as part of a controlled trial.

Synchronous malignant multicentric cerebral glioma with atypical neuroradiological presentation and comparatively long survival: Case report and literature review

Introduction. Synchronous multicentric cerebral gliomas are uncommon brain tumors, mostly malignant, with unknown pathogenesis, unfavorable prognosis and still controversial management. Preoperative differentiation from other multiple brain pathologies by conventional magnetic resonance imaging (MRI) is often difficult, but supplemental use of advanced magnetic resonance techniques should allow the tumor biology to be predicted and an appropriate treatment strategy planned. Case report. We reported a 59-yearold man with double synchronous multicentric cerebral lesions, which had initial MRI and diffusion-weighted imaging presentation as left parietal metastasis and ipsilateral amygdalo- hippocampal low-grade glioma. However, magnetic resonance spectroscopy (MRS) of both lesions showed different metabolite profiles of malignant glioma. En bloc resection of the easily accessible parietal lesion revealed glioblastoma with methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. Subsequently, the patient was treated with temozolomide (TMZ)-based chemoradiation according to Stupp?s protocol, with continuous standard (5/28) adjuvant TMZ in 12 courses. Despite prolonged stabilization of the disease with good life-quality during treatment, the patient died 19 months after diagnosis. The time to tumor progression estimated by MRI was 17 months. Conclusion. MRS significantly improved the differential diagnostic accuracy of conventional MRI in our patient. In accordance with reviewed literature data, the younger age, good initial performance status and methylated MGMT gene promoter were all favorable predictors of longer survival in the reported case. Resection of at least one easily accessible tumor lesion, followed by TMZ-based chemoradiation, with continuous adjuvant TMZ in more than 6 standard courses, seems currently to be the most beneficial therapeutic option for such cases.

Assessment of endoscopic treatment for quadrigeminal cistern arachnoid cysts: A 7-year experience with 28 cases.

Quadrigeminal cistern arachnoid cysts (QACs) are difficult to treat because of their deep location and the presence of nervous and vascular structures of the pineal-quadrigeminal region. There are several surgical procedures available for QACs, including craniotomy and cyst excision or fenestration, ventriculoperitoneal or cystoperitoneal shunting, and endoscopic fenestration. There is a debate about which method is the best. The aim of this study is to evaluate the effectiveness and safety of endoscopic ventriculocystostomy (VC) and third ventriculostomy (ETV) for treatment of arachnoid cysts of the quadrigeminal cistern. Twenty-eight patients with QACs who had undergone endoscopic treatment in our department between August 2007 and June 2014 were studied retrospectively. Patient age at the time of endoscopic treatment ranged from 5 months to 42 years, including 25 children (14 males and 11 females) and 3 adults (one male and two females). All patients presented with hydrocephalus and did not undergo shunting prior to neuroendoscopic surgery. The first endoscopic procedures included lateral ventricle cystostomy (LVC) together with ETV in 18 cases, third ventricle cystostomy (3rd VC) together with ETV in 3 cases, and double VC (3rd VC and LVC) together with ETV in 7 cases. Data were obtained on clinical and neuroradiological presentation, indications to treat, surgical technique, complications, and the results of clinical and neuroradiological follow-up. Complete success was achieved in 25 (89.3 %) of 28 cases. During the follow-up period, one case underwent endoscopic reoperation with success. Shunts were implanted in 2 patients due to progression of symptoms and increase in hydrocephalus after the first endoscopic operation. Shunt independency was achieved in 26 (92.9 %) of 28 cases. The cyst was reduced in size in 22 cases (78.6 %). Postoperative images showed a reduction in the size of the ventricles in 23 cases (82.1 %). There was no surgical mortality. Subdural collection developed in 4 cases (14.3 %) and required a transient subduroperitoneal shunt in 2 cases, whereas the other 2 patients were asymptomatic and did not require any surgical treatment. VC together with ETV through precoronal approach is an effective treatment for symptomatic QACs and should be the initial surgical procedure. The surgical indications should include signs of elevated ICP (including increased head circumference), Parinaud syndrome, gait ataxia, and nystagmus. Also, surgery is indicated by progressive enlargement of the cyst and young children with large cysts even if the patients are asymptomatic. Contraindications to surgery include the absence of symptoms (older children and adult) and isolated developmental delay. The main criterion for successful surgery should be improvement of clinical symptoms instead of reduced cyst volume and/or ventricular size. Repeated endoscopic procedures may be considered only for the patients whose symptoms improved after first endoscopic operation.

Neuromyelitis Optica: Atypical Clinical and Neuroradiological Presentation

The extreme variability of clinical and MRI findings in the suspicion of Devic's disease always requires the detection of specific antibodies (AQP4). MRI scans were performed with a high-field MRI scanner (1.5T General Electric Signa Horizon): the MRI protocol of the brain employed axial DP, T2, T1, FLAIR and DWI weighted images (wi) and coronal T2-wi. After intravenous administration of contrast medium axial and sagittal T1-weighted images of the brain were repeated. The spine protocol employed after contrast medium included sagittal T2-wi, T2-wi with fat suppression and T1-wi. In May 2004, a 64-year-old healthy Caucasian woman began to suffer loss of motor and thermal sensitivity in the left lower limb. MRI showed non-specific areas of abnormal signal intensity on the deep left frontal and right frontoparietal white matter with no pathological enhancement after contrast medium and a small intramedullary area of altered signal at metameric level C2-C4 with a diagnosis of post-viral transverse myelitis. The patient had two similar episodes years later so the neurologist decided to search for circulating IgG AQP4 with the definitive diagnosis of neuromyelitis optica. In this case, compared to a clinical presentation of atypical deficit neurological involvement, the neuroradiological results of a progressive diffuse involvement of the white matter were atypical.

Diagnostic features and outcome of surgical therapy of acromegalic patients: experience of the last three decades.

Transsphenoidal (TNS) surgery remains the primary therapeutic option for GH-secreting pituitary adenomas. The aims of this study were to verify the impact of TNS surgery on treatment of acromegaly before and after identification by a dedicated neurosurgical team and to enumerate diagnostic features of the disease described over three decades. 41 patients (group A) who underwent TNS surgery by a dedicated neurosurgical team (2000-2008) and 126 patients (group B) operated on by surgeons not specialized in pituitary surgery (1979-1999) were retrospectively analyzed. No significant differences were observed between the two groups in terms of delay of diagnosis, mean basal GH levels and GH nadir values, prevalence of hypopituitarism and hypertension. IGF-I SDS were significantly higher, while prevalence of IGT/diabetes was significantly lower in group B than in group A. Overall remission rate after surgery was 58.5% for group A (75% in microadenomas and 48% in macroadenomas, P=NS) and 37% for group B (P<0.05 vs group A; for microadenomas, 34% vs 75% of group A, P<0.05, for macroadenomas, 36% vs 48% of group A, P=NS). The mean delay of diagnosis was 4.9 and 5.9 years in group A and B, respectively. Our data confirm that a dedicated neurosurgical team is needed in order to improve remission rates in acromegalic patients. No changes in biochemical, clinical and neuroradiological presentation of disease were observed over the last three decades. As the high prevalence of macroadenomas negatively influences surgical cure, earlier diagnosis should be considered as mandatory to achieve a better outcome.

Neuroimaging findings in the initial phase of development of high grade cortical astrocytomas

ObjectivesTo describe the neuroradiological characteristics of a series of high grade cortical astrocytomas in the initial phase of development and their pattern of growth during a short time period. Material and methodsThis was a retrospective observational study of the neuroradiological findings in six patients diagnosed with high grade astrocytoma. All presented with a new onset epileptic seizure and focal supratentorial cortical lesions. The diagnosis was established after a short period of clinical and radiological follow-up. ResultsMagnetic resonance imaging (MRI) detected a small cortical lesion that was hyperintense in T2-weighted sequences in all six patients. This lesion showed slight or moderate enhancement after the administration of a contrast agent in five patients. All six patients underwent follow-up MRI within six months of the initial MRI examination (mean 79 days). Follow-up MRI showed marked growth of the lesions in all cases, and the histological diagnosis of high grade astrocytoma (glioblastoma in five patients and anaplastic oligoastrocytoma in one) was established after surgical debulking. ConclusionHigh grade astrocytomas originating in the supratentorial cortex can have an atypical neuroradiological presentation in the early stages. High grade astrocytoma should be included in the differential diagnosis of a cortical lesion that enhances slightly or moderately after the administration of contrast material in a patient with a new onset epileptic seizure.

Hallazgos neurorradiológicos en la fase inicial del desarrollo de astrocitomas corticales de alto grado de malignidad

ObjectivesTo describe the neuroradiological characteristics of a series of high grade cortical astrocytomas in the initial phase of development and their pattern of growth during a short time period. Material and methodsThis was a retrospective observational study of the neuroradiological findings in six patients diagnosed with high grade astrocytoma. All presented with a new onset epileptic seizure and focal supratentorial cortical lesions. The diagnosis was established after a short period of clinical and radiological follow-up. ResultsMagnetic resonance imaging (MRI) detected a small cortical lesion that was hyperintense in T2-weighted sequences in all six patients. This lesion showed slight or moderate enhancement after the administration of a contrast agent in five patients. All six patients underwent follow-up MRI within six months of the initial MRI examination (mean 79 days). Follow-up MRI showed marked growth of the lesions in all cases, and the histological diagnosis of high grade astrocytoma (glioblastoma in five patients and anaplastic oligoastrocytoma in one) was established after surgical debulking. ConclusionHigh grade astrocytomas originating in the supratentorial cortex can have an atypical neuroradiological presentation in the early stages. High grade astrocytoma should be included in the differential diagnosis of a cortical lesion that enhances slightly or moderately after the administration of contrast material in a patient with a new onset epileptic seizure.

LGI1 related limbic encephalitis and response to immunosuppressive therapy

Limbic encephalitis (LE) is characterized by a subacute onset of episodic memory impairment, disorientation, agitation, seizures and histological evidence of mesial temporal lobe inflammation. It is usually considered to have a paraneoplastic origin and is associated with specific autoantibodies in various cancers [1]. The non-paraneoplastic form has similar clinical and neuroradiological presentation. In these cases antibodies usually target voltage-gated potassium channels (VGKC) or glutamic acid decarboxylase and are, therefore, accepted as immunotherapyresponsive syndromes. Potassium channel antibodies were reported in two patients with reversible LE for the first time in 2001 [2]. Very recently, however, Dalmau et al. showed that the autoantigen associated with LE previously attributed to VGKC is, in fact, leucine-rich, glioma inactivated 1 (LGI1), a neuronal secreted protein [3]. Since this is a relatively rare condition, there have been very few publications on the clinical findings, treatment and follow-up results in this group of patients [3–6] and the optimum treatment regimen is still unknown. In this case report we present a young male patient who did not respond to plasma exchange therapy, but improved rapidly and significantly after IV pulse steroid infusion. A 31-year-old man was admitted for confusional state that had started 1 month ago. He had fever, vomiting and headache at the onset. His past medical history was unremarkable. Physical and neurologic examinations were normal apart from confusion and short-term memory deficits. Cranial MRI revealed hyperintense signals in bilateral hippocampi and the amygdaloid nuclei with little contrast enhancement (Fig. 1). At the onset of his complaints he was admitted to another hospital where he was diagnosed with herpes encephalitis and was given acyclovir without any benefit. In our clinic, blood studies including complete blood count, liver and renal function tests, tumor markers and paraneoplastic antibody analysis (anti-Hu, -Yo, -Ri, -Ma, -CV2) were all normal. Serum electrolyte analysis revealed mild hyponatremia (132 mEq/L). Cerebrospinal fluid (CSF) protein and glucose levels were normal. Analysis of CSF cytology showed increased mononuclear cells. Herpes PCR was negative. Thorax– abdomen CT scans, scrotal-pelvic ultrasonography and whole body fluorodeoxyglucose-positron emission tomography were negative for malignancy. He had two temporal lobe seizures during his follow up. Electroencephalography revealed bilateral generalized mild slow wave paroxysms, without epileptiform discharges. The patient was put on oxcarbazepine (OXC), and did not have any further seizures. In order to investigate the presence of nonparaneoplastic LE, serum and CSF samples were sent to Dr. J. Dalmau’s laboratory where antibodies for NMDA receptors and VGKC antibodies were studied. Meanwhile, the patient had six exchanges of 1.5 plasma volumes on alternate days. We could not give intravenous immunoglobulin (IVIg) because his IgA levels were very low. No clinical response was obtained in the first week after treatment with plasmapheresis and the patient was discharged from hospital. One month later we were informed that he had antibodies against LGI1. The patient was hospitalized again for IV pulse steroid treatment. At that time, his orientation in time and space had partially improved; however, he still had severe memory deficits. He had difficulty in remembering some recent events. After the B. Kaymakamzade T. Kansu E. Tan N. Dericioglu (&) Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey e-mail: noroloji2011@gmail.com

Assessment of endoscopic treatment for middle cranial fossa arachnoid cysts

Endoscopic cystocisternotomy is one of three surgical methods used to treat middle cranial fossa arachnoid cysts. There is debate about which method is the best. The aim of this study is to evaluate the effectiveness and safety of endoscopic cystocisternotomy for treatment of arachnoid cysts of the middle cranial fossa. Thirty-two patients with arachnoid cysts of the middle cranial fossa who had undergone endoscopic cystocisternal fenestration between 2004 and 2009 were studied retrospectively. Data were obtained on clinical and neuroradiological presentation, indications to treat, surgical technique, complications, and the results of clinical and neuroradiological follow-up. Among the 27 patients with symptoms before surgery, 8 had disappearance of symptoms and 17 had improvement of symptoms. The cyst was reduced in size or it completely disappeared in 24 (75%) patients. The incidence rate of complications was 18.8%. Endoscopic cystocisternal fenestration is an effective treatment for symptomatic arachnoid cysts of the middle cranial fossa and should be the initial surgical procedure.

Endoscopic treatment of middle fossa arachnoid cysts

To investigate and evaluate the effectiveness of neuroendoscopic therapy for arachnoid cysts of middle cranial fossa. From January 2004 to June 2009, 32 patients with arachnoid cysts of middle cranial fossa who were treated with endoscopic cystocisternal fenestration were retrospectively analyzed. There were 21 male patients and 11 female patients, aged from 6 months to 39 years. The clinical and neuroradiological presentation, indications, surgical technique, complications, and clinical and neuroradiological follow-up were analyzed. The cysts were reduced in size in 20 patients and completely disappeared in 4 patients. For the 27 patients with symptoms before operation, the symptoms disappeared in 8 cases and improved in 17 cases after operation. There were asymptomatic subdural hydroma in 4 patients, intracranial infection and incision cerebro-spinal fluid leakage in 1 patient respectively. The complication incidence rate was 18.8%. Endoscopic fenestration is an effective treatment for symptomatic arachnoid cysts of middle cranial fossa and could be performed as the first surgical choice for these patients.

Novel splice‐site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy

Infantile neuroaxonal dystrophy, INAD, is a severe progressive psychomotor disorder with infantile onset and characterized by the presence of axonal spheroids throughout the central and peripheral nervous systems. A subset of INAD patients shows also brain iron accumulation which represents instead the distinctive feature of the idiopathic neurodegeneration with brain iron accumulation, NBIA. These diseases share the same causative gene, PLA2G6, encoding iPLA2-VIA, a calcium-independent phospholipase. Mutations that lead to a complete absence of protein are associated with a severe INAD profile, while compound heterozygous mutations with possibly a residual protein activity are instead associated with the less severe NBIA phenotype. Here we describe two INAD patients both with an unusually rapid disease progression and a peculiar neuroradiological presentation in one of them. Compound heterozygosity for a large intragenic deletion and a nonsense mutation was found in one of them while the other is carrying two novel splice-site mutations. Breakpoint-sequence analysis suggests a non-allelic-homologous-recombination (NAHR) event, probably underlying the rearrangement. These findings, while supporting the genotype-phenotype correlation already observed in INAD patients, provide the first sequence characterization of a genomic rearrangement in PLA2G6 gene, thus orienting the search for missing mutant alleles in PLA2G6 related diseases.

A Giant Bilateral Calcified Chronic Subdural Hematoma

A calcified chronic subdural hematoma is a rare disease and its neuroradiological presentation is variable. The degree of calcification extends from thin calcified inner membranes to dense calcification and even ossification of the hematoma. Previous reports described a maximum of two hematoma cavities with calcified inner hematoma membranes. Neuroimaging report with illustrative computerized tomography images. A patient with a bilateral symptomatic calcified chronic subdural hematoma, or so-called "armoured brain", was admitted to our intensive care unit with clinical signs of increased intracranial pressure. Computerized cranial tomography demonstrated multiple bilaterally located hematoma cavities with thin calcified inner membranes. After neurosurgical intervention by bilateral burr hole trepanation, clinical symptoms improved. Our case of a calcified chronic subdural hematoma presents with an uncommon imaging pattern with more than four hematoma cavities bounded by predominantly convex- and concave-configured thin calcified inner membranes.

Endoscopic treatment of middle fossa arachnoid cysts: a series of 40 patients treated endoscopically in two centres

Middle fossa arachnoid cysts (MFAC) are a relatively common, benign pathology that pose a therapeutic challenge for both symptomatic and asymptomatic patients. The optimal surgical strategy and indication to treat are still debated by neurosurgeons. We reviewed our experience and results in a group of patients treated with endoscopic fenestration with the aim to assess indications to treat and clinical and neuroradiological results. The data on 40 patients operated with endoscopic fenestration for MFAC in two centres, "Anna Meyer" Children's Hospital, Florence, Italy, and Royal Liverpool Children's Hospital "Alder Hey", Liverpool, UK, between 2001 and 2007 were retrospectively reviewed with prospective follow-up. We analysed clinical and neuroradiological presentation, indications to treat, surgical technique, complications, and clinical and neuroradiological follow-up. There were 30 males and ten females: mean age, 7.8 years; mean follow-up, 21 months. The neuronavigation system was used in 12 patients in the English cohort. Thirty-seven patients (92.5%) had a satisfactory clinical outcome. The cyst was reduced in size or completely disappeared in 29 patients (72.5%). There was no death or significant morbidity associated with the procedure. Four patients required further surgical treatment. Four patients experienced a post-traumatic intracystic bleeding after surgery. Compared to microsurgical fenestration and cyst shunting, our experience with endoscopic fenestration was as effective and safe but less invasive. Each case must be assessed with its individual characteristics to define the optimal surgical strategy. Successful treatment may not reduce the risk of post-traumatic head injury haemorrhage.

NDUFS4 mutations cause Leigh syndrome with predominant brainstem involvement

Complex I deficiency is a frequent cause of Leigh syndrome. We describe a non-consanguineous Ashkenazi–Sephardic Jewish patient with Leigh syndrome due to complex I deficiency. The clinical and neuroradiological presentation showed predominant brainstem involvement. Blue native polyacrylamide gel electrophoresis analysis revealed an impaired assembly of complex I. The patient was found to be compound heterozygous of two mutations in the NDUFS4 gene: p.Asp119His (a novel mutation) and p.Lys154 fs (recently described in an Ashkenazi Jewish family). These findings support the suggestion that the p.Lys154 fs mutation in NDUFS4 should be evaluated in Ashkenazi Jewish patients presenting with early onset Leigh syndrome even before enzymatic studies. Our results further demonstrated that NDUFS4 presents a hotspot of mutations in the genetic apparatus of oxidative phosphorylation and the correct assembly of the subunit it encodes is essential for completion of the assembly of complex I.

Melanocytoma in the orbital apex

We report a case of a 49-year-old man presenting with a melanocytoma located in the orbital apex. The tumor was subtotally removed and adjuvant chemotherapy was given. The patient has remained under follow-up for the past 12 years without any evidence of recurrence. Although the characteristic neuroradiological images of the lesion prove the presence of melanin, histological examination is crucial to establish the diagnosis of melanocytoma. Besides the clinical and neuroradiological presentation, the histological, immunohistochemical, and ultrastructural findings are described. To our knowledge, this is the second published case of intraorbital melanocytoma initially confined to the orbital apex. Melanocytoma should be included in the differential diagnosis of intraorbital tumors in such a location.

Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature

Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibre accumulation. Following the identification of glial fibrillary acidic protein (GFAP) gene as the causative gene, cases of adult-onset AD (AOAD) are being described with increasing frequency. AOAD has a different clinical and neuroradiological presentation with respect to early-onset AD, as abnormalities are mainly concentrated in the brainstem-spinal cord junction. We report detailed clinical and genetic data of 11 cases of AOAD, observed over a 4-year period, and a review of the previously reported 25 cases of genetically confirmed AOAD. In our series, onset occurred as late as age 62, and up to 71 in an affected deceased relative. Most cases appeared sporadic, but family history may be misleading. The most frequent symptoms were related to bulbar dysfunction-with dysarthria, dysphagia, dysphonia (seven patients)-, pyramidal involvement (seven patients) and cerebellar ataxia (seven patients). Four patients had palatal myoclonus. Sleep disorders were also observed (four cases). Bulbar symptoms, however, were infrequent at onset and two symptomatic patients had an almost pure pyramidal involvement. Two subjects were asymptomatic. Misdiagnosis at presentation was frequent and MRI was instrumental in suggesting the correct diagnosis by showing, in all cases, mild to severe atrophy of the medulla oblongata extending caudally to the cervical spinal cord. In ten patients, molecular studies revealed six novel missense mutations and three previously reported changes in GFAP. The last typical patient carried no definitely pathogenic mutation, but a missense variant (p.D157N), supposedly a rare polymorphism. Revision of the literature and the present series indicate that the clinical picture is not specific, but AOAD must be considered in patients of any age with lower brainstem signs. When present, palatal myoclonus is strongly suggestive. Pyramidal involvement, cerebellar ataxia and urinary disturbances are common. Less frequent findings include sleep disorders and dysautonomia. Fluctuations may occur. The course is variable, usually slowly progressive and less severe than the AD forms with earlier onset. AOAD is more common than previously thought and might even be the most common form of AD. The diagnosis is strongly suggested by MRI and confirmed by GFAP gene analysis.

A series of patients with subpial hemorrhage: Clinical manifestation, neuroradiological presentation and therapeutic implications

Subpial hemorrhage is a rare finding in patients with a variable spectrum of neurological symptoms and signs. Here we present a series of 10 patients with subpial hemorrhage, 53 to 80 years old, diagnosed and treated within the last 4 years at a single center. Patients were identified based on imaging criteria with either magnetic resonance imaging (MRI) or computed tomography (CT) showing blood along the cortical surface. Presenting symptoms were diverse, with seizures being the most frequent followed by headaches and focal neurological signs such as sensory or motor deficits. Of 7 patients undergoing lumbar puncture, none showed fresh blood or cerebrospinal fluid (CSF) xanthochromia. Neither digital subtraction angiography (DSA) nor MR venography (MRV) confirmed cerebral vein thrombosis as a possible etiologic factor for subpial hemorrhage. Patients for whom follow-up was available (n=8), showed complete recovery indicating an excellent prognosis. Overall, the etiology of subpial hemorrhage remains obscure. Treatment should be symptomatic with particular attention to antiepileptic medication.