Primary Neurologic Involvement Research Articles

The clinical and radiological features and prevalence of Neuro-Behçet's Disease: A retrospective cohort multicenter study in Saudi Arabia

BackgroundNeuro-Behçet's disease (NBD) is defined as primary neurological involvement in patients with systemic symptoms of BD. The variety of clinical presentations seen in NBD and the long list of similar conditions make diagnosis challenging. This retrospective study aimed to estimate the prevalence and describe neurological involvement in patients with Behçet's disease who presented to King Abdulaziz Medical Cities in Jeddah and Riyadh, Saudi Arabia. MethodsThis was a retrospective, cohort study which utilized a non-probability consecutive sampling technique to include all patients diagnosed with NBD patients. All patients with BD (215) were screened for neurological symptoms. Thirty-five patients were found to be diagnosed with NBD. Outcomes were estimated using the modified Rankin scale (mRS). ResultsIn our cohort, one in six patients with BD was diagnosed with NBD. A total of 35 patients were diagnosed with NBD (mean age 27.56 ± 10.36 years; [2.88:1; Male: Female]). The main clinical features of NBD were headaches, weakness, unsteadiness, and dysarthria. The most commonly involved sites on imaging were the brainstem, diencephalon, cerebellum and basal ganglia. Oligocolonal bands were negative in all patients. Maintenance therapy most commonly included oral corticosteroids, azathioprine, and/or infliximab. Most patients received pulse corticosteroids alone when presenting with acute relapse. Half of our cohort was asymptomatic and three in four had favorable outcomes. ConclusionNBD is common among patients with BD in our population with most patients having favorable outcomes. Patients might have a wide array of symptoms which might make the diagnosis challenging.

Isolated Papilledema Revealing Behçet's Disease: Case Report and Literature Review

Neuro-Behçet’s disease (NBD) is defined as the primary neurological involvement seen in patients with Behçet's disease (BD). It can be classified as parenchymal or non-parenchymal involvement, with variable manifestation that can be confused with other neuroinflammatory conditions of the nervous system. Papillitis is an inflammation of the optic disk that most often manifests itself with a papilledema. This condition seems to be exceptional during BD, especially as an initial presentation. We report the observation of a neuro-Behçet in a 30-year-old woman who presented with an isolated bilateral papillary edema.

Pathophysiological Mechanisms in Neurodevelopmental Disorders Caused by Rac GTPases Dysregulation: What's behind Neuro-RACopathies.

Rho family guanosine triphosphatases (GTPases) regulate cellular signaling and cytoskeletal dynamics, playing a pivotal role in cell adhesion, migration, and cell cycle progression. The Rac subfamily of Rho GTPases consists of three highly homologous proteins, Rac 1–3. The proper function of Rac1 and Rac3, and their correct interaction with guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs) are crucial for neural development. Pathogenic variants affecting these delicate biological processes are implicated in different medical conditions in humans, primarily neurodevelopmental disorders (NDDs). In addition to a direct deleterious effect produced by genetic variants in the RAC genes, a dysregulated GTPase activity resulting from an abnormal function of GEFs and GAPs has been involved in the pathogenesis of distinctive emerging conditions. In this study, we reviewed the current pertinent literature on Rac-related disorders with a primary neurological involvement, providing an overview of the current knowledge on the pathophysiological mechanisms involved in the neuro-RACopathies.

Brain-related outcome measures in trials recruiting critically-ill children.

Randomized controlled trials leading to innovations that improve outcomes in acute life-threatening illnesses in children are scarce. A key issue is how we refocus research on outcomes that matter and are more relevant to those making emergency decisions, and those involved with managing and living with the late-outcome. We have used information from recent trials in critically ill children - in particular those illnesses without any primary neurologic involvement - to develop an approach to brain-related outcomes that will maximize child and family benefit from research. Fifteen recent pediatric critical care trials illustrate four types of brain-related outcomes assessment: death or organ-system-failures - as illustrated by studies in systemic illness; neurological and neuropsychological outcomes - as illustrated by the glycemic control studies; cognitive outcomes - as illustrated by a sedative trial; and composite outcomes - as illustrated by the therapeutic hypothermia studies. The 15 research trials point to five areas that will need to be addressed and incorporated into future trial design, including use of: neurologic monitoring during intensive care unit admission; postdischarge outcomes assessments; strategies to improve retention in long-term follow-up; child and family-centered outcomes; and core outcomes datasets.

Behçet’s Disease and Neuro-Behçet’s Syndrome

Behçet’s disease is an idiopathic chronic relapsing multisystem vascular-inflammatory disease of unknown origin, which usually presents with orogenital ulceration and uveitis and is identified as the triple-symptom complex. Primary neurological involvement in Behçet’s disease is known as neuro-Behçet’s syndrome (NBS). Clinical findings and neuroimaging demonstrate that there are two major forms of NBS: a central nervous system inflammatory parenchymal disease, and a less common nonparenchymal form that involves the large extraparenchymal vascular structures, mainly the venous dural sinuses. Cranial magnetic resonance imaging (MRI) typically reveals brainstem lesions with parenchymal involvement and an occluded dural sinus may be seen in the extraparenchymal type. Cerebrospinal fluid studies typically indicate inflammatory changes in the parenchyma and increased pressure with extraparenchymal involvement. Drugs used for the preventive treatment of NBS include azathioprine, cyclophosphamide, and anti-TNF agents.

Behçet's Syndrome and Nervous System Involvement.

Although Behçet's syndrome (BS) is classified as a rare disease in European countries and the USA, its neurologic involvement "neuro-Behçet's syndrome (NBS)" is commonly included in the differential diagnosis of many inflammatory and vascular central nervous system (CNS) disorders. Clinical and neuroimaging findings support two major forms of NBS: parenchymal NBS (p-NBS) and an extra-parenchymal form that presents with cerebral venous sinus thrombosis (CVST). The present review summarizes recent findings on the etiopathogenesis and clinico-radiological features of this disorder as well as its treatment options. Recent laboratory and clinical findings include the discovery of antibodies to human and mouse neuro-fibrils showing cross-reactivity with Streptococcus spp. and Mycobacterium tuberculosis heat shock proteins (HSP) in NBS. Diagnostically, two distinct magnetic resonance imaging (MRI) patterns of spinal cord involvement have been observed: (a) "Bagel sign" and (b) "motor neuron" patterns. Therapeutic studies have shown that infliximab effectively prevents further relapses and stabilizes the symptoms of patients experiencing ongoing clinical relapses while being treated with single or multiple immunosuppressant drugs. Primary neurological involvement referred to as NBS. The majority of patients with NBS present with parenchymal involvement that commonly affects the brain stem-diencephalic region. Headache, dysarthria, ataxia, and hemiparesis are the main clinical features of NBS.

Chapter 53 - Von Hippel–Lindau disease and Sturge–Weber syndrome

The primary neurologic involvement in both von Hippel-Lindau (VHL) disease and Sturge-Weber syndrome (SWS) is vascular tumor/vascular malformation, but molecular pathogenesis, long-term symptom evolution, and treatment are quite different. VHL is caused by dominant inherited or de novo germline mutations, while SWS is caused by somatic mosaicism. A diagnosis of VHL carries substantial cancer risk, while the clinical issues in SWS are primarily related to the consequences of the intracranial vascular abnormalities.

Usefulness of Tokuhashi Score in Survival Prediction of Patients Operated for Vertebral Metastatic Disease

Introduction Spinal metastasis can produce pain, deformity, neurological compromise, and, therefore, decrease survival quality and expectancy. Surgical management is usually indicated for pain control, neurological decompression, and to avoid deformity progression. To identify the best operative option, the type of tumor, the systemic involvement, and patient clinical condition are determinants. Tokuhashi et al created a scoring system to estimate survival and to stratify surgical treatment based on well-established parameters. Our objective was to evaluate the usefulness of Tokuhashi scoring (TS) system by comparing the predicted and real survival times. Materials and Methods From 2004 to 2011, 96 patients with vertebral metastasis, consecutively operated by the same surgical team, were enrolled and retrospectively analyzed in this study. Patients included have a known primary tumor, were older than 18 years, had no previous related surgery, and were preoperatively evaluated with the Tokuhashi score. Six patients without confirmed date of death were excluded. Hematopoietic tumors were not considered metastatic lesions. Primary tumor, tumoral location, neurological involvement, Tokuhashi score, complications, and survival time were evaluated. In all cases radiograph, CT scan, and magnetic resonance imaging were assessed. Patients' average age was 59 years and main tumor locations were as follows: kidney (25%), lung (19%), and breast (19%). Results Group 1 included 45 patients with a scoring prediction of less than 6 months survival (TS 0–8), 7 patients from this group survived more than 6 months, correspondence was 84.4%. In Group 2, with 27 patients with a scoring prediction between 6 and 12 months (TS 9–11), 2 patients survived less than 6 months and 11 more than 12 months, with 51.8% correspondence. Group 3, with 18 patients, and a predicted survival of more than 12 months (TS 12–15) had 100% correspondence. The Tokuhashi general correspondence rate was 77.7%. Sensitivity and specificity of Tokuhashi score were 77.7% and 88.8%, respectively, with a positive predictor value of 77.7%. According to the most frequent primary tumor diagnosis, survival time was 19 months for breast, 28 for thyroid, 26.5 for prostate, and 5.1 for lung, with a mean survival time of 15 months. Correspondence rates related to primary tumor were 82% in lung, 78% in kidney, and 65% in breast, respectively. Conclusion In our series, the Tokuhashi general correspondence was 77.7%; similar results were found in the original and revised Tokuhashi reports, and other authors found a lower correspondence, nevertheless, most of them included hematopoietic tumors. The lower correspondence observed in Group 2 (51,8%) was negatively influenced by the most common primary tumor in this group, breast carcinoma, with 65%, compared with lung 82% and kidney 78%. For our practice, Tokuhashi scoring constitutes a useful tool to predict survival, with a sensitivity and specificity of 77.7% and 88.8%, respectively. Breast tumors positively influenced by medical treatment have less correspondence than other tumors and should be considered on case-by-case basis.

A cross-sectional electromyography assessment in linear scleroderma patients.

BackgroundMuscle atrophy and asymmetric extremity growth is a common feature of linear scleroderma (LS). Extra-cutaneous features are also common and primary neurologic involvement, with sympathetic dysfunction, may have a pathogenic role in subcutaneous and muscle atrophy. The aim was investigate nerve conduction and muscle involvement by electromyography in pediatric patients with LS.MethodsWe conducted a retrospective review of LS pediatric patients who had regular follow up at a single pediatric center from 1997–2013. We selected participants if they had consistently good follow up and enrolled consecutive patients in the study. We examined LS photos as well as clinical, serological and imaging findings. Electromyograms (EMG) were performed with bilateral symmetric technique, using surface and needle electrodes, comparing the affected side with the contralateral side. Abnormal muscle activity was categorized as a myopathic or neurogenic pattern.ResultsNine LS subjects were selected for EMG, 2 with Parry-Romberg/Hemifacial Atrophy Syndrome, 7 linear scleroderma of an extremity and 2 with mixed forms (linear and morphea). Electromyogram analysis indicated that all but one had asymmetric myopathic pattern in muscles underlying the linear streaks. Motor and sensory nerve conduction was also evaluated in upper and lower limbs and one presented a neurogenic pattern. Masticatory muscle testing showed a myopathic pattern in the atrophic face of 2 cases with head and face involvement.ConclusionIn our small series of LS patients, we found a surprising amount of muscle dysfunction by EMG. The muscle involvement may be possibly related to a secondary peripheral nerve involvement due to LS inflammation and fibrosis. Further collaborative studies to confirm these findings are needed.

PReS-FINAL-2124: Electromyography assessment in localized scleroderma

Localized Scleroderma (LS) has been associated with central and peripheral nervous system involvement. Facial palsy, extra-ocular movement disorders, trigeminal neuralgia and hemi-masticatory spams are described as primary neurologic involvement. Romberg hypothesized that sympathetic regulation has pathogenic relevance in facial hemiatrophy, which was reproduced experimentally by superior cervical ganglion ablation (Resende LA et al. 1991).

Characteristics of headaches in cases diagnosed with neuro-behcet's disease

Introduction and aims: Behcet's disease is a vascular-inflammatory chronic disease with an obscure pathogenesis./INS; Primary neurological involvement is in the form of non-structural headache (migrainous HA), subclinical NBS, cerebral dural sinus vein thrombosis (extra axial), MSS involvement (intraaxial), neuro-/INS;psycho-behcet and peripheral nervous involvements.

Editorial overview: lysosomal storage disorders with primary neurological involvement

The focus of this issue of the Journal of Inherited Metabolic Disease is on lysosomal storage diseases (LSD) subtypes associated with primary neurological involvement. Conceptual advances that have had practical applications will be highlighted in this review issue. Although rare, LSDs are a global problem and represent life-limiting or threatening disorders that can have a significant impact on patients’ wellbeing. We have chosen experts from around the world, whose experience reflect the forefront in medical genetics devoted to progress in the LSDs. In the course of soliciting articles on the topic, it became apparent that use of certain terms required clarification. Although several publications have described LSD variants with primary neurological involvement as neuropathic or neuronopathic forms of the disease, strictly speaking this choice of terms is misplaced. In our copy of Pryse-Phillips’ Companion to Clinical Neurology (1995), neuropathy is defined as a disorder of one or more peripheral nerves, whereas neuronopathy is used to refer to a disease of the peripheral nervous system in which primary neuropathological changes appear in the nerve cell body rather than the axon of the myelin sheath. As peripheral nerve pathology is seen in only a subset of LSDs, the term neurodegenerative was suggested as a more appropriate descriptor, which may be acceptable but perhaps not for all entities (e.g., mucolipidosis IV). In the end, and for the sake of brevity, it was decided the term neuropathic would be retained, but discussion of disorders would not cover topics relating to secondary neurologic complications (e.g., radiculopathy secondary to vertebral compression in osteoporotic patients with Gaucher disease). Over the past few decades, we have witnessed remarkable progress in our understanding of LSD; a group of inborn errors of metabolism characterized by a disruption in the degradation, processing and/or transport of various molecules that represent by-products of cellular turnover. The article by Jardim and colleagues, presented in two formats—a review in print and a detailed description of individual clinical entities in an electronic version as supplementary material—describes the various modes of clinical presentation. It is evident that, historically, examination of the phenotype has not included systematic analysis of disease course in ways that enable quantitative assignment of disease severity or rate of progression. Furthermore, studies that have attempted to correlate clinical expression with the genotype have repeatedly pointed to the lack of perfect concordance, except in a few cases, and there remain limited investigations of the factors that influence age of onset or specific patterns of neuronal vulnerability. Recent interest in the neurological problems noted in patients with Gaucher disease type 1 (GD1, conventionally viewed as the non-neuronopathic form) has prompted re-evaluation of the phenotype and investigations of putative causal links, if any, and in particular, the relationship between GD1 and risk for Parkinsonism and/or peripheral neuropathy. Along these lines, the paper by Cherin and co-workers describe observations garnered from a national (French) cross-sectional observational survey. G. M. Pastores (*) Departments of Neurology and Pediatrics, New York University School of Medicine, New York, USA e-mail: Gregory.Pastores@nyumc.org

The spectrum of nervous system involvement in Behçet’s syndrome and its differential diagnosis

Behçet's Syndrome (BS) is a multi-system, vascular-inflammatory disease of unknown origin, involving the nervous system in a subgroup of patients. The growing clinical and imaging evidence suggests that primary neurological involvement in BS may be subclassified into two major forms: the first one, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system (CNS) disease, with focal or multifocal parenchymal involvement mostly presenting with a subacute brainstem syndrome and hemiparesis; the other, which has few symptoms and a better neurological prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension. These two types rarely occur in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a nonstructural vascular type headache is relatively common and independent from neurological involvement. Neurologic complications secondary to systemic involvement of BS such as cerebral emboli from cardiac complications of BS and increased intracranial pressure due to superior vena cava syndrome, as well as neurologic complications related to BS treatments such as CNS neurotoxicity with cyclosporine and peripheral neuropathy with the use of thalidomide or colchisin are considered as secondary neurological complications of this syndrome. As the neurological involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and response to treatment. Currently, treatment options are limited to attack and symptomatic therapies with no evidence for the efficacy of any long term preventive treatment.

Analysis of isolated cranial nerve manifestations in patients with cancer

The aim of this study was to assess the underlying causes of isolated cranial nerve (CN) manifestations in cancer patients. In a prospective study over a 16 month period, 20 of 242 patients presented with isolated CN manifestations, and were assessed for the following: primary site; CN symptoms and signs; length of time between primary diagnosis and neurological involvement; and survival following the neurological diagnosis. The most frequent primary site was determined as hematological malignancy (9/20). Thirteen of the 20 patients presented with single CN manifestations. Underlying causes of CN manifestations in 16 of the 20 patients were related to metastases. They included meningeal carcinomatosis (10/16), brain stem metastases (3/16), primary brain astrocytomas (1/16), and metastases out of the central nervous system (2/16). The remaining four patients' CN manifestations related to non-metastatic conditions. Although most of the isolated CN manifestations were due to systemic metastasis, in particular to the meninges, up to 20% were related to benign conditions.

Abnormal neuronal metabolism and storage in mucopolysaccharidosis type VI (Maroteaux–Lamy) disease

Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy disease, is an inherited disorder of glycosaminoglycan catabolism caused by deficient activity of the lysosomal hydrolase, N-acetylgalactosamine 4-sulphatase (4S). A variety of prominent visceral and skeletal defects are characteristic, but primary neurological involvement has generally been considered absent. We report here that the feline model of MPS VI exhibits abnormal lysosomal storage in occasional neurones and glia distributed throughout the cerebral cortex. Abnormal lysosomal inclusions were pleiomorphic with some resembling zebra bodies and dense core inclusions typical of other MPS diseases or the membranous storage bodies characteristic of the gangliosidoses. Pyramidal neurones were shown to contain abnormal amounts of GM2 and GM3 gangliosides by immunocytochemical staining and unesterified cholesterol by histochemical (filipin) staining. Further, Golgi staining of pyramidal neurones revealed that some possessed ectopic axon hillock neurites and meganeurites similar to those described in Tay-Sachs and other neuronal storage diseases with ganglioside storage. Some animals evaluated in this study also received allogeneic bone marrow transplants, but no significant differences in neuronal storage were noted between treated and untreated individuals. These studies demonstrate that deficiency of 4S activity can lead to metabolic abnormalities in the neurones of central nervous system in cats, and that these changes may not be readily amenable to correction by bone marrow transplantation. Given the close pathological and biochemical similarities between feline and human MPS VI, it is conceivable that children with this disease have similar neuronal involvement.

A continuum of phenotypes in Gaucher disease

Gaucher disease results from an inherited deficiency of the lysosomal enzyme glucocerebrosidase and the subsequent accumulation of glucocerebroside in macrophages. This produces systemic problems. Traditionally, Gaucher disease has been classified in three clinically defined types. Type 1 involves no primary neurologic involvement. Type 2 is the acute neuropathic form. These patients have progressive brain stem dysfunction leading to death. Type 3 is a chronically progressive form presently between infancy and adolescence. This has a broad range of phenotypic presentation.

Ocular Motor Abnormalities in Gaucher Disease

Gaucher disease (GD) without primary neurological involvement (GD1) is now treatable with exogenous enzyme replacement therapy (ERT). ERT does not halt the fatal neurological progression of type 2 (infantile) disease (GD2), but in type 3 disease (GD3), neurological progression may be slowed down or possibly halted in some cases by higher doses of ERT. Therefore, it is crucial to distinguish between GD1 and GD3 disease for appropriate treatment. Saccade initiation failure (SIF) (ocular motor apraxia, supranuclear gaze palsy) is often the earliest neurological sign in GD3. This sign can be difficult to detect clinically, but is readily revealed as missed quick-phases during induced optokinetic and vestibular nystagmus. We investigated whether objective ocular motor assessment could improve the detection of GD3 disease. Eight children, diagnosed enzymatically with GD, were tested using D.C.-electro-oculography and/or video. In 6 children, optokinetic and vestibular nystagmus showed marked paucity of quick-phases making the eyes "lock up" at the limit of gaze, thus indicating SIF. In 3 cases the diagnosis was revised from GD1 to GD3. The diagnosis of GD3 was made in two children who were too ill for clinical assessment of SIF. Only 1 child had previous clinical evidence of SIF, and so GD3 was confirmed. One child was normal and the diagnosis of another remains uncertain. These results show that the possibility of SIF and hence GD3 may not be excluded by clinical examination alone. Thus we recommend that, where possible, objective eye movement assessment be carried out in children with GD.

Neurologic Complications of Graft-Versus-Host Disease

BMT has become an important therapy for many hematologic disorders. Following BMT, the recipient may develop GVHD when it appears that immunocompetent donor lymphocytes react to host antigens. Acute and chronic GVHD represent two distinct syndromes. Acute GVHD has not been associated with primary neurologic involvement. Polymyositis has been reported in 12 patients with chronic GVHD, with the most common underlying illness being aplastic anemia. The clinical, serologic, and muscle biopsy features of the myositis in GVHD have been similar to those observed in idiopathic polymyositis. Weakness was moderate to severe and responded to prednisone, sometimes with the addition of azathioprine. Prognosis depended upon the underlying disease and not on the severity of the myositis. MG occurs rarely in chronic GVHD. Most patients with MG and GVHD have had aplastic anemia; those with aplastic anemia are more likely to have anti-AchR prior to BMT. The clinical manifestations of GVHD MG have not differed from classic autoimmune MG; each patient had elevated antiacetylcholine receptor antibodies titers. All patients have responded well to cholinesterase inhibitors but have received other immunosuppressants. These observations suggest that aplastic anemia is an important host factor in the development of the autoimmune disorders seen with chronic GVHD, certainly of myositis and MG. Herpes zoster peripheral nerve infections have occurred in patients with chronic GVHD. One patient had mononeuritis multiplex. In both acute and chronic GVHD, CNS impairment is usually caused by metabolic encephalopathy or infection. Primary CNS involvement has not been recognized.

Clinicopathologic study of thirty-three fatal cases of Asian influenza.

THE 1957 pandemic of Asian influenza was associated with a high attack rate and excess pneumonia mortality1; influenza-associated deaths were most common at the extremes of life. Although case fatality rates were low, the course of some cases was fulminant2 3 4 5 and comparable with the rapidly lethal variety of influenza observed in the pandemic of 1918–206 and in several subsequent epidemics.7 Recent reports of deaths associated with Asian influenza2 3 4 5 , 8 9 10 11 12 describe explosive, rapidly progressive and unresponsive respiratory failure frequently associated with staphylococcal infection, primary influenzal pneumonitis, neurologic and cardiac involvement, the rare isolation of Haemophilus influenzae from the respiratory tract and . . .