Diffuse Central Nervous System Research Articles

How useful is EEG and EEG monitoring in the acutely ill and how to interpret it?

How useful is EEG and EEG monitoring in the acutely ill and how to interpret it?

Clinical Evaluation and Diagnosis of Severe Epilepsy Syndromes of Early Childhood

The developing brain is particularly susceptible to seizures. Diffuse central nervous system pathology or injury in early infancy, when the brain is most vulnerable, may lead to catastrophic epilepsies such as Ohtahara's epileptic encephalopathy and early myoclonic epileptic encephalopathy. These epileptic encephalopathies are difficult to treat and have poor prognoses. As the brain undergoes programmed synaptogenesis, apoptosis, and myelination, the epilepsy phenotypes and electroencephalography (EEG) findings change, producing age-dependent epileptic encephalopathies. Specifically, as they grow older, 40% to 60% of infants with infantile spasms and a concomitant hypsarrhythmia on EEG will develop Lennox-Gastaut syndrome with tonic and atonic seizures, associated with a synchronous, generalized 1.5- to 2-Hz spike and slow wave discharges on EEG. In the context of age-dependent epileptic encephalopathies, as an epilepsy syndrome is evolving, it is often difficult to accurately diagnose the specific epilepsy syndrome in a young child who presents with seizures. It is the clinical evolution of the seizure types and the EEG that helps the clinician make an accurate diagnosis. As more is known about the underlying pathophysiology for the various epilepsy syndromes, not only the clinical picture and EEG but also a genetic blood test will be used to accurately diagnose a specific epilepsy syndrome. A case in point would be severe myoclonic epilepsy of infancy (classically known as Dravet syndrome) and severe myoclonic epilepsy of infancy-borderland/ borderline, which are associated with specific mutations in the sodium ion channel gene SCN1A.

Sarcocystis sp. encephalomyelitis in a cat

: A 5‐month‐old male neutered domestic shorthair cat was evaluated for spinal pain, ataxia, and anisocoria. Neuroanatomic localization indicated diffuse or multifocal central nervous system disease. On cerebrospinal fluid analysis, neutrophilic pleocytosis and intracellular protozoal merozoites were observed. The merozoites were oval, 2–4 μm in width and 4–6 μm in length, and had linear arrays of nuclear material concentrated at one pole. Serum was positive for Sarcocystis sp. antibodies and negative for Toxoplasma gondii antibodies. The organism was determined to be either Sarcocystis neurona or Sarcocystis dasypi based on sequence analysis of the internal transcribed spacer 1 ribosomal RNA genomic region. Clinical disease resolved following treatment with 3 different protocols for protozoal infection. This case is the first to demonstrate the antemortem diagnosis and survival of a domestic cat with Sarcocystis sp.‐associated encephalomyelitis. Clinicians and cytopathologists should include Sarcocystis sp. as a differential for feline inflammatory central nervous system disease characterized by neutrophilic pleocytosis.

Fellow eye changes in optic neuritis correlate with the risk of multiple sclerosis

Background Recent studies demonstrate early diffuse central nervous system (CNS) inflammation in patients with multiple sclerosis (MS). The clinically unaffected (fellow) eye of patients with unilateral optic neuritis (ON) may reflect the status of normal-appearing white matter in the CNS, which can be assessed electrophysiologically. Objective To study the relationship between electrophysiological parameters in the fellow eye of ON patients, and risk of conversion to MS. Methods Forty-eight consecutive patients with acute unilateral ON were examined 12 months after ON of which 14 had MS, 19 remained high risk (HR) for MS, and 15 had low risk (LR) for MS according to McDonald’s criteria. Twenty-five age-matched controls were also tested. Amplitude and latency of multifocal visual evoked potential (mfVEP) in the fellow eyes of patients at 12 months were analyzed and compared with controls. Results Average mfVEP amplitude was 240 ± 35, 232 ± 36, 181 ± 38, and 169 ± 48 nV for controls, LR, HR, and MS groups respectively. Average mfVEP latency for controls, LR, HR, and MS patients was 139.7 ± 5.5, 141.7 ± 3.6, 145.9 ± 8.9, and 152.0 ± 9.9 ms respectively. Conclusions The magnitude of latency prolongation and amplitude decline 12 months after the initial episode was proportional to the risk of MS. The prognostic significance of these changes as predictors of subsequent MS should be investigated longitudinally.

Neuropsychiatric Involvement in Systemic Lupus Erythematosus:Current Therapeutic Approach

The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their usefulness in the treatment of neuropsychiatric SLE. This article reviews the clinical approach to therapy in patients with SLE and neuropsychiatric involvement.

Timing of Therapeutic Intervention Determines Functional and Survival Outcomes in a Mouse Model of Late Infantile Batten Disease

Classical late infantile neuronal ceroid lipofuscinosis (cLINCL) is a monogenic disorder caused by the loss of tripeptidyl peptidase 1 (TPP1) activity as a result of mutations in CLN2. Absence of TPP1 results in lysosomal storage with an accompanying axonal degeneration throughout the central nervous system (CNS), which leads to progressive neurodegeneration and early death. In this study, we compared the efficacies of pre- and post-symptomatic injections of recombinant adeno-associated virus (AAV) for treating the cellular and functional abnormalities of CLN2 mutant mice. Intracranial injection of AAV1-hCLN2 resulted in widespread human TPP1 (hTPP1) activity in the brain that was 10-100-fold above wild-type levels. Injections before disease onset prevented storage and spared neurons from axonal degeneration, reflected by the preservation of motor function. Furthermore, the majority of CLN2 mutant mice treated pre-symptomatically lived for at least 330 days, compared with a median survival of 151 days in untreated CLN2 mutant controls. In contrast, although injection after disease onset ameliorated lysosomal storage, there was evidence of axonal degeneration, motor function showed limited recovery, and the animals had a median lifespan of 216 days. These data illustrate the importance of early intervention for enhanced therapeutic benefit, which may provide guidance in designing novel treatment strategies for cLINCL patients.

Blockade of TREM‐2 exacerbates experimental autoimmune encephalomyelitis

Triggering receptor expressed on myeloid cells (TREM-2) is a membrane receptor associated with DAP12 that is expressed primarily in myeloid cells, including dendritic cells and microglia, and promotes fusion of osteoclast precursors into multinucleated cells. A rare autosomal recessive condition, Nasu-Hakola disease (NHD) is associated with loss-of-function mutations in DAP12 and TREM-2. The brain pathology observed in NHD patients suggests that disruption of the TREM-2/DAP12 pathway leads to neurodegeneration with demyelination and axonal loss. In this study, we have characterized TREM-2 protein expression on microglia using a newly produced monoclonal antibody directed against the mouse TREM-2 receptor. We report that TREM-2 expression is up-regulated in the spinal cord during both the early inflammatory and chronic phases of myelin oligodendrocyte glycoprotein (MOG)(35-55)peptide-induced experimental autoimmune encaphalomyelitis (EAE). We also demonstrate that TREM-2 is highly expressed on microglial cells in the central nervous system (CNS) during EAE and that blockade of TREM-2 during the effector phase of EAE results in disease exacerbation with more diffuse CNS inflammatory infiltrates and demyelination in the brain parenchyma. These results demonstrate a critical role for TREM-2 during inflammatory responses in the CNS.

Late onset vanishing white matter disease

Sirs: Vanishing white matter disease (VWM; MIM# 603896) or childhood ataxia with diffuse central nervous system hypomyelination (CACH) is a progressive leukodystrophy beginning usually in early childhood [7]. Common clinical findings include cerebellar ataxia, spasticity, epileptic seizures, severe cognitive decline and a progressive course with rapid deterioration following stress conditions such as minor head trauma, febrile infections or fright [13]. Neuropathological abnormalities indicate a selective disruption of oligodendrocytes and astrocytes with sparing of neurons [1, 14]. VWM is an autosomal recessive disease caused by mutations in each of the five genes (EIF2B1 – EIF2B5) encoding the eukaryotic translation initiation factor 2B (eIF2B) [5]. So far 77 different mutations have been identified, two-thirds affecting the epsilon subunit (eIF2B5) [2]. EIF2B mutations are speculated to lead to increased susceptibility to various physiological stress conditions [4, 6]. The identification of the genetic defect led to the recognition of a wider phenotypical spectrum of VWM. Here we report the case of a 36 year old man who was admitted because of rapid progressive cognitive decline and a complex movement disorder. The patient had a history of infrequent generalized tonic-clonic seizures since the age of 14 years. Two years later mild right sided hemiparesis of unknown cause was recognised by a neurologist but no imaging was performed. However, the patient recognised no handicap and development was otherwise normal. After finishing junior high school he worked as a tool maker until the age of 35 years. Then, rapid deterioration occurred shortly after a bicycle accident. Eighteen months later the patient became bedridden. Clinical examination revealed encephalopathy with frontal lobe symptoms including slowness, apathy and positive grasp reflex. Mini Mental Status Examination revealed dementia with 22 of 30 points. Motor signs included severe ataxia, spasticity more pronounced in lower limbs and dystonia as well as choreoathetotic movements of arms and hands. He was no longer able to stand or walk unassisted and needed help for almost all activities of daily living. He died in a vegetative state 24 months after onset of deterioration. Magnetic resonance imaging (MRI) of the brain at the age of 36 years showed severe symmetric leukencephalopathy suggestive of VWM: Cystic breakdown of cerebral white matter and replacement by CSF was present predominantly in the deep frontal white matter but also involving the subcortical U-fibres. There was no gadolinium enhancement of the lesions (Figure 1A and B). MR spectroscopy revealed an almost complete loss of all main white matter metabolites (Figure 1C). Screening of the genes encoding eIF2B demonstrated the homozygous missense mutation p.His113Arg in the e-subunit (eIF2B5). As in a few other reports this mutation is associated with milder forms of VWM [11, 12]. In contrast, different mutations like the Cree mutation (Arg195His in eIF2B5) are associated with most severe courses of the disease [2]. Our observation provides further evidence that VWM also may manifest as adult-onset leukodystrophy and should be considered in complex movement disorders with cognitive decline even if obvious disease starts as late as 35 years of age. In addition to our MR spectroscopy findings two papers report on lactate and glucose in VWM spectra [3, 8]. However, this seems to be not specific, but rather due to partial volume effects and these findings most likely represent CSF rather than pathological brain tissue contribution. Since similar MR spectra as in our case are found in childhood onset cases of VWM [9, 10] it is likely that extensive loss of white matter metabolites represents a hallmark in neuroimaging of the disease independent of onset age.

New-onset acute symptomatic seizure in a neurological intensive care unit

New-onset acute symptomatic seizures can be the presenting feature of acute neurological diseases. The etiological spectrum of new-onset acute symptomatic seizures and outcome may be different in developing countries when compared to developed countries. To study the clinical profile of new-onset acute symptomatic seizures as the first presenting event in patients with acute neurological illness in a neurological intensive care unit (NICU) in a developing country. Prospective study in a NICU in a tertiary care hospital. Consecutive patients with acute symptomatic new-onset seizure admitted to NICU in a tertiary care hospital over a period of 28 months. The etiology was determined by neuroimaging and appropriate investigations including cerebrospinal fluid examination. Of the 3,151 admissions, 66 (2.1%) were related to new-onset acute symptomatic seizures as the first presentation. The mean age was 49.07 + 20.20 years. Tonic-clonic, generalized tonic-clonic or partial seizure with or without secondary generalization were the seizure type. At presentation 52 (79%) patients had single seizure, 10 (15%) patients had seizure clusters and four (6%) patients presented with status epilepticus (SE). The major etiological risk factors were central nervous system (CNS) infections (32%), metabolic disorders (32%) and cerebrovascular diseases (21%). In the NICU 10 (15%) patients had early seizure recurrence and three (4.5%) developed SE. Of these 13 patients, in nine (69%) patients the pathology was infection-related and the other commonality was involvement of cortical gray matter. Factors associated with seizure recurrence or SE were focal cerebral lesions involving cortical gray matter or diffuse cerebral pathology, meningoencephalitis. In 69% of these patients the pathology was infection-related. There were only two deaths, both in patients with SE and related to the underlying etiology. The risk of seizure recurrence and SE after the first acute symptomatic seizure is likely to be high in patients with acute focal cerebral lesions and diffuse CNS infections. The commonality in both the pathologies is cortical gray matter involvement.

Severe, fetal‐onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?

We present three siblings with a precise onset of fetal seizure-like activity who had severe olivopontocerebellar hypoplasia (OPCH) and degeneration. Autopsies at 20, 27, and 37 weeks gestation showed diffuse central nervous system volume loss that was most marked for the cerebellum and brain stem structures. Neuropathological abnormalities included dysplastic, C-shaped inferior olivary nuclei, absent or immature dentate nuclei, and cell paucity more marked for the cerebellar vermis than the hemispheres. Delayed development was seen in layer 2 of the cerebral cortex and in Purkinje cells of the cerebellum. Prenatal monitoring defined a developmental window of 16-18 weeks gestation when ultrasonic assessment of cerebellar width was used for prenatal diagnosis. We discuss our findings in the context of the differential diagnosis for infantile (O)PCH and propose a classification scheme for the pontocerebellar hypoplasias. These patients represent the earliest reported with OPCH and provide unique information regarding the developmental neuropathology of this condition.

Oligodendroglial Dysplasia in Two Bullmastiff Dogs

Leukodystrophies are inherited neurological disorders involving central nervous system white matter. They are uncommon in animals but a few, breed-specific entities have been described. In 2002, two young-adult, purebred Bullmastiff dogs from central New York State presented to their referring veterinarians displaying moderate to severe ataxia of all limbs, spastic tetraparesis that was worse in the pelvic limbs, and a diffuse, action-related, whole-body tremor. Clinical signs were insidious in onset and slowly progressive. Anatomic diagnoses considered were a C1-C5 lesion or, based on the whole-body tremor, a diffuse central nervous system disorder. No gross lesions were apparent in the brain or spinal cord. Histopathologically, numerous, multifocal, sharply demarcated, small, ovoid to angular areas of myelin pallor (plaques) were present throughout the major white matter tracts of the brainstem and spinal cord. These plaques, which often were traversed by axons, did not stain with luxol fast blue for myelin and were associated with minimal astrocytosis. Ultrastructural findings include occasional hypertrophic glia in white matter, rare unmyelinated segments of axons, and focal proliferation of tubule-containing cytoplasmic glial cell processes (oligodendroglial). The described clinical and morphological findings and age of onset are similar to the well-characterized, presumably hereditary, bovine syndrome known as Charolais ataxia or oligodendroglial dysplasia. This article presents the first description of a leukodystrophy in the Bullmastiff breed and the first report of oligodendroglial dysplasia in animals other than Charolais cattle.

MRI evidence for multiple sclerosis as a diffuse disease of the central nervous system

The classical view of MS as a chronic inflammatory demyelinating disease leading to the formation of focal central nervous system (CNS) white matter (WM) lesions has been recently challenged by pathological studies and by the extensive application of modern MRI-based techniques. There is now overwhelming evidence supporting the following statements: MS causes widespread tissue damage in the normal-appearing white matter (NAWM) of the brain and spinal cord, whose extent and severity is more strictly associated to the clinical manifestations of the disease than the extent of focal pathology. Discrete, macroscopic lesions are just the tip of the iceberg of MS pathology. Grey matter (GM) damage is a consistent feature of all MS phenotypes, which is progressive from the start of the relapsing-remitting phase of the disease. As is the case for WM, GM damage is also a mixture of focal lesions and diffuse pathology. High-field strength MR scanners are improving our ability to image focal GM lesions and modern MR-based techniques are enabling us to quantify in vivo the extent and severity of GM pathology, which have been shown to correlate only moderately with the amount of WM changes. At least part of GM pathology in MS is not secondary to retrograde degeneration of fibers traversing WM lesions. The neurodegenerative component of the disease is not a late phenomenon and it is not completely driven by inflammatory demyelination. In fact, neurodegeneration occurs very early in the course of MS and the correlation between MRI measures of inflammation and neurodegeneration is weak in all disease phases. The interplay of inflammation and neurodegeneration is a complex and still poorly understood phenomenon. At least part of MS-related neurodegeneration is not directly driven by Wallerian degeneration. Functional cortical changes can be seen in virtually all MS patients and are likely to play a central role in the ability of the MS brain to respond to tissue injury and, hence, limit the functional consequences of structural damage. MS disability is not just the result of tissue destruction but rather a balance between tissue destruction, tissue repair and adaptive cortical reorganization. All of this calls for the concept of MS as a focal, inflammatory demyelinating, WM disease to be reexamined and to start viewing MS as a diffuse CNS disease with an important neurodegenerative component. This is central for identifying novel and effective treatment strategies.

Angiotrophic large cell lymphoma mimicking multiple sclerosis associated transverse myelitis.

Angiotrophic large cell lymphoma (ALCL) is a rare disease characterized by a proliferation of malignant lymphoid cells, usually of B-cell origin, within the lumina of small vessels and frequently involving the central nervous system (CNS). ALCL generally follows a rapidly fatal course and is rarely diagnosed prior to autopsy. Tumour cells are rarely present on examination of peripheral blood, cerebrospinal fluid (CSF) or bone marrow, therefore, an early diagnosis is heavily dependent on recognition of neurological manifestations which are present in over 80% of cases. A pre-mortem diagnosis of ALCL can be made in cases where brain biopsy has been performed. We report a case of a 45-year-old woman demonstrating clinical and laboratory features suggestive of multiple sclerosis associated transverse myelitis (MSA-TM) in whom ALCL was unexpectedly discovered at autopsy. Microscopic examination revealed diffuse CNS vascular involvement by neoplastic cells and prominent myelopathy of the upper thoracic spinal cord associated with ascending and descending tract degeneration of the spinal motor and sensory tracts. Neoplastic cells were immunoreactive for B-cell lymphoid markers. The present case is the first to demonstrate neoplastic B-cell clonality in ALCL using polymerase chain reaction (PCR) to detect abnormal V-D-J immunoglobulin gene rearrangements. ALCL should be considered in the differential diagnosis whenever a transverse myelitis is present in association with global encephalopathy and elevated serum lactate dehydrogenase. The neurological manifestations of ALCL with particular reference to its presentation as MSA-TM is discussed. Copyright 1999 Harcourt Publishers Ltd.

Brain transplantation of genetically engineered human neural stem cells globally corrects brain lesions in the mucopolysaccharidosis type VII mouse

In the present study, we investigated the feasibility of using human neural stem cells (NSCs) in the treatment of diffuse central nervous system (CNS) alterations in a murine model of mucopolysaccharidosis VII (MPS VII), a lysosomal storage disease caused by a genetic defect in the beta-glucuronidase gene. An immortalized NSC line derived from human fetal telencephalon was genetically engineered to overexpress beta-glucuronidase and transplanted into the cerebral ventricles of neonatal MPS VII mouse. Transplanted human NSCs were found to integrate and migrate in the host brain and to produce large amount of beta-glucuronidase. Brain contents of the substrates of beta-glucuronidase were reduced to nearly normal levels, and widespread clearing of lysosomal storage was observed in the MPS VII mouse brain at 25 days posttransplantation. The number of engrafted cells decreased markedly after the transplantation, and it appears that the major cause of the cell death was not the immune response of the host but apoptotic cell death of grafted human NSCs. Results showed that human NSCs would serve as a useful gene transfer vehicle for the treatment of diffuse CNS lesions in human lysosomal storage diseases and are potentially applicable in the treatment of patients suffering from neurological disorders.

Parent pointers☆

We hypothesized that intellectual, neurodevelopmental, and visual-motor tests would be able to characterize the scope and nature of central nervous system involvement in children with congenital central hypoventilation syndrome. Age-appropriate intellectual (Brazelton Neonatal Behavioral Assessment, Bayley Scales of Infant Development, Wechsler Preschool and Primary Scale of Intelligence—Revised and Wechsler Intelligence Scale for Children—Revised), neurodevelopmental (Halsted-Reitan neuropsychologic battery), and visual-motor (Beery visual-motor integration test) tests were given to 17 children with congenital central hypoventilation syndrome (age 0.1 to 14.3 years). We found a broad range in IQ and developmental quotient, from greater than the 85th percentile to less than the 5th percentile, with discrepancies noted between verbal and performance measures. Multiple asymmetries and deficiencies of motor performance, not consistently related to handedness, were also found. Significant eye-hand coordination deficits were uncommon, but general performance was well below average. Full, verbal, and performance IQs and developmental quotients ≥70 and <70 were compared by chi-square analysis with other associated conditions, including hours of ventilatory support, duration of initial hospitalization, growth, pulmonary hypertension, seizures, brain atrophy, central and peripheral hearing deficits, and ophthaimologic abnormalities; no statistically significant associations were found. These results lend support to the hypothesis that congenital central hypoventilation syndrome is a diffuse central nervous system process. However, the effects of transient hypoxia and associated conditions on neurodevelopmental test results cannot be excluded with certainty.

Central nervous system involvement in autoimmune polyglandular syndrome

We present a 33 year-old man, admitted because of transient deterioration of visual acuity. Magnetic resonance imaging showed diffuse central nervous system (CNS) demyelination, which largely resolved spontaneously within 4 months. The patient fulfilled the diagnostic criteria of APS type III, having autoimmune thyroiditis and alopecia universalis. In this patient, autoimmune activation against CNS antigens is thought to be the cause of reversible CNS demyelination.

CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease.

CCL2 is a member of the CC chemokine family that mediates the migration and recruitment of monocytes and T cells and has been identified in the central nervous system (CNS) during several neuroinflammatory diseases. In order to examine the biological effect of constitutive CCL2 expression in the CNS, the authors engineered a mouse that expressed CCL2 in the CNS under control of the human glial fibrillary acidic protein (hGFAP) promoter. The results demonstrated that transgenic expression of CCL2 in the CNS resulted in diffuse CNS monocyte infiltration and accumulation. Transgenic CCL2 expression did not alter normal development, differentiation, or function of T cells. There was no evidence of overt CNS disease or other pathologic phenotype when mice were left unchallenged with antigen or uninfected. However, when CCL2 transgenic mice were given a peripheral challenge of lipopolysaccharide (LPS), an inflammatory infiltrate with organized perivascular lesions developed. Infection of the transgenic mice with Theiler’s murine encephalomyelitis virus (TMEV) resulted in accelerated onset and increased severity of clinical and histological disease. These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease.

Bilateral ophthalmic artery occlusion in a patient with aquired immunodeficiency syndrome and central nervous system lymphoma

Purpose Clinical course and autopsy findings in a patient with human immunodeficiency virus-1 immunodeficiency, central nervous system lymphoma, and bilateral, simultaneous ophthalmic artery occlusions. Design Observational case report. Methods Clinical examination, fundus photography, gross and microscopic pathologic study. Results Fundus photographs disclosed stasis in retinal arterioles, the absence of a cherry-red spot; internal carotid arteriography disclosed bilateral ophthalmic artery occlusions; postmortem histopathologic examination disclosed bilateral ophthalmic artery atherosclerosis, retinal ischemic necrosis, ischemic optic neuropathy, diffuse large-cell lymphoma of multiple areas of the central nervous system, cytomegalovirus encephalitis, atherosclerosis, and bronchopneumonia. Conclusions A 47-year-old male with aquired immunodeficiency syndrome, profound immunodeficiency, systemic hypertension, and central nervous system lymphoma, developed deep vein thrombosis, bilateral ophthalmic artery occlusions, and died of pneumonia 7 weeks after the onset of blindness. Postmortem study revealed bilateral ophthalmic artery hemorrhagic atherosclerosis, ischemic optic neuropathy, ischemic retinal necrosis, diffuse large-cell central nervous system lymphoma, cytomegalovirus encephalitis, pneumonitis, and systemic atherosclerosis.

Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE).

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves a wide range of focal and diffuse central and peripheral nervous system disorders and affects up to 75% of SLE patients. NPSLE can occur any time in the course of SLE, even during periods in which no SLE disease activity is detected, and is likely to be caused by multiple factors, including autoantibody production, microvasculopathy and pro-inflammatory cytokines. Central to the diagnosis of NPSLE is the question of whether the presenting neuropsychiatric symptoms are due to SLE-mediated organ dysfunction, infection, medication side-effects or metabolic abnormalities (e.g. uraemia), or are due to an unrelated condition. The diagnostic inference of NPSLE can be made only after these secondary causes have been excluded. There is no one single diagnostic tool specific to NPSLE, and clinical diagnostic impressions must be based on the combined use of immunoserological testing, functional and/or structural neuroimaging and standardized neurological, rheumatological, psychiatric and neuropsychological assessments. The management of NPSLE includes symptomatic and/or immunosuppressive treatment strategies depending on the specific presenting neuropsychiatric symptoms and whether these occur in the setting of an SLE disease activity flare.

Episodic coma in a new leukodystrophy

Among the leukodystrophies of a hypomyelinating nature, childhood ataxia with diffuse central nervous system hypomyelination exhibits the unique feature of rapid decrease in mental status after relatively minor head injuries or otherwise noncomplicated febrile illnesses. This article reports the case of a child with progressive spastic quadriparesis in whom unconsciousness developed repeatedly as a result of minor head trauma and required prolonged critical-care nursing. Although cognition is believed to be relatively preserved in this disorder, this child developed progressive cognitive decline. A detailed review of the literature is presented along with discussion of the potential mechanisms of neurologic deterioration.