Ivana Vodopivec

Teaching research methodology in medical schools: students' attitudes towards and knowledge about science

Objective  To explore the relationship between teaching scientific methodology in Year 2 of the medical curriculum and student attitudes towards and knowledge about science and scientific methodology.

Academic misconduct among medical students in a post-communist country

Aim  To assess the prevalence of, attitudes towards and willingness to report different forms of academic dishonesty among medical students in a post‐communist transitional country.

Clinical features, diagnostic findings, and treatment of Susac syndrome: A case series

BACKGROUND Susac syndrome (SS) is a rare, presumed autoimmune condition characterized by the clinical triad of branch retinal artery occlusions (BRAOs), encephalopathy, and sensorineural hearing loss. The aim of this study was to evaluate clinical features, diagnostic results, treatment, and outcomes in SS. METHODS Five patients with SS were referred to three tertiary care centers in Boston. The observation period across these patients was 7-57months. RESULTS At initial presentation, none of the patients demonstrated the complete triad of BRAO, sensorineural hearing loss, and encephalopathy. The interval between symptom onset and diagnosis of SS was 4-30weeks. Brain MRI findings thought to be characteristic of SS (including callosal fluid-attenuated inversion recovery (FLAIR) hyperintense and T1 hypointense lesions) were frequently absent. Microinfarcts noted on diffusion-weighted imaging (DWI), BRAOs and vessel wall hyperfluorescence on fluorescein angiography (FA) were present in all cases in the acute encephalopathic phase. All patients treated with glucocorticoids and intravenous immunoglobulins (IVIg) alone experienced further clinical progression until additional immunosuppressive therapy was instituted. CONCLUSIONS The rarity of SS, its incomplete and variable presentation, and the nonspecific imaging findings invariably led to delayed diagnosis. DWI and FA should be used to identify the acute microvascular injury and monitor treatment response. Immunomodulatory agents more potent than glucocorticoids and IVIg might be required to control the disease.

Treatment of Susac Syndrome

Opinion statementSusac syndrome is a microangiopathy of the brain, retina, and cochlea. Several lines of evidence support the concept that this disease is an acquired autoimmune disorder. Prospective, randomized, controlled studies of treatments are not available because the disease is rare. Furthermore, the average period of follow-up in reported cases is short, limiting a complete understanding of the natural history of the disease. Empirical treatment strategies are therefore based upon expert recommendations and anecdotal reports of response to various immunomodulators, and the appropriate duration of therapy is not known. In our opinion, the encephalopathic form of Susac syndrome should be treated early and aggressively to avoid cognitive dysfunction and disability. Induction therapy with pulse methylprednisolone frequently proves to be inadequate. Additional agents, including intravenous immunoglobulins, intravenous cyclophosphamide, or rituximab are often necessary to induce a sustained remission. Maintenance therapy with oral glucocorticoids combined with intravenous immunoglobulins, mycophenolate mofetil, methotrexate, azathioprine, cyclophosphamide, or rituximab is typically necessary to achieve a sustained remission. Aspirin may be used as an adjunctive agent, although evidence showing efficacy is scant. The response to treatment should be closely monitored by frequent clinical examinations, brain MRI, and fluorescein angiography. Once disease remission has been established, it appears prudent to continue maintenance treatment for at least two additional years, although the real long-term risk of future relapses remains unknown. Establishing a multicenter patient registry and biorepository is essential to study the pathogenesis of the disease, further define the duration of disease, identify reliable biomarkers that aid early diagnosis and assess risk of relapse, and develop effective disease-specific therapies.

Treatment of neuromyelitis optica.

Purpose of review Neuromyelitis optica (NMO) is an antibody-mediated inflammatory disease of the central nervous system with a predilection for the optic nerves, spinal cord and certain brain regions. It has a distinct pathogenesis relating to aquaporin-4 autoimmunity and complement-mediated injury. This knowledge has translated into targeted efforts to develop novel, disease-specific treatments. In this review, we discuss evidence supporting the use of currently available treatments for acute exacerbations and for long-term disease modification. We also discuss the risks and benefits of available and emerging immunotherapies. Recent findings Early, accurate diagnosis of NMO with appropriate acute and long-term immunosuppressive treatment is of prime importance for the prevention of disability associated with this disease. Standard measures for the management of acute exacerbations include intravenous methylprednisolone and plasmapheresis. First-line, long-term immunotherapies for NMO include azathioprine, mycophenolate mofetil and rituximab. Three randomized controlled treatment trials evaluating these agents are currently being conducted. In addition, there are numerous emerging therapies that are based upon current understanding of the disease immunopathogenesis. Summary NMO is an autoimmune disease that is separate from multiple sclerosis. Better understanding of its antibody and complement-dependent pathophysiology has proven to be critical for the formulation of current and future treatment strategies.

A 44‐year‐old man with eye, kidney, and brain dysfunction

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, autosomal dominant condition caused by mutations of TREX1 (3‐prime repair exonuclease‐1). The phenotypic expressions range from isolated retinal involvement to varying degrees of retinopathy, cerebral infarction with calcium depositions, nephropathy, and hepatopathy. We report a case of RVCL caused by a novel TREX1 mutation. This patients multisystem presentation, retinal involvement interpreted as “retinal vasculitis,” and improvement of neuroimaging abnormalities with dexamethasone led to the accepted diagnosis of a rheumatologic disorder resembling Behçet disease. Clinicians should consider RVCL in any patient with retinal capillary obliterations associated with tumefactive brain lesions or nephropathy. Ann Neurol 2016;79:507–519

Ocular inflammation in neurorheumatic disease.

Neuroimmunologic and systemic rheumatic diseases are frequently accompanied by inflammation of the eye, ocular adnexa, and orbital tissues. An understanding of the diverse forms of ophthalmic pathology in these conditions aids the clinician in making appropriate preventative, diagnostic, therapeutic, and prognostic decisions. In this review, the authors address ocular inflammation in neurorheumatic disease in three sections: first, they highlight current perspectives on immune mechanisms in the development of these disorders; next, they provide a framework for the recognition and evaluation of ophthalmologic inflammatory entities; finally, they discuss in detail several inflammatory conditions that affect the nervous system and the eye, emphasizing the features that should alert neurologists to initiate ophthalmologic evaluation. The conditions discussed include multiple sclerosis, neuromyelitis optica, chronic relapsing inflammatory optic neuropathy, Susac syndrome, Cogan syndrome, acute posterior multifocal placoid pigment epitheliopathy, Vogt-Koyanagi-Harada disease, Behçet disease, sarcoidosis, systemic lupus erythematosus, granulomatosis with polyangiitis (Wegener granulomatosis), polyarteritis nodosa, giant cell arteritis, IgG4-related disease, and Sjögren syndrome.

A neurologist's guide to safe use of immunomodulatory therapies.

Increased understanding of the pathogenesis of immune-mediated neurologic conditions with concomitant development of new therapeutic agents modulating various aspects of the immune system has resulted in the use of innovative therapies in the treatment of these diseases. These novel immunomodulatory therapeutic regimens also augment the potential for complications, including severe adverse effects.In this review, the authors address practical issues regarding management of patients with neuroimmunological conditions treated with immunomodulatory therapies, including glucocorticoids, methotrexate, azathioprine, mycophenolate, cyclophosphamide, rituximab, tumor necrosis factor-α inhibitors, and intravenous immunoglobulins. Particular focus is placed on their infectious and noninfectious adverse effects, contraindications, safety monitoring, risk surveillance, and preventive strategies in clinical practice.

A Cluster of CNS Infections Due to B. cereus in the Setting of Acute Myeloid Leukemia: Neuropathology in 5 Patients

Abstract Bacillus cereus typically causes a self-limited foodborne gastrointestinal (GI) illness. Severe invasive infection occurs rarely, mainly among immunocompromised hosts. We describe a cluster of B. cereus infections among 5 patients with acute myeloid leukemia and chemotherapy-induced neutropenia. The initial case presented with occipital lobe abscess and was found on biopsy to have organisms consistent with Bacillus species. Within 1 week, a second patient died of fulminant brain swelling and hemorrhage. Neuropathologic autopsy and culture revealed B. cereus; hospital infection control and public health officials were notified. Three more patients died within the subsequent 9 months (2 patients had rapid massive hemorrhage and many bacilli reminiscent of Bacillus anthracis infection, and 1 patient had sparse bacilli, petechial hemorrhages, and border zone infarcts). Blood cultures yielded positive results in 3 of 5 cases. A possible route of infection was hematogenous dissemination via GI mucosal breaches (GI symptoms occurred in 3 of 5 cases, and postmortem GI ulceration was found in 3 of 4 cases). Bacilli were seen in 2 of 3 GI ulcerations. Epidemiologic work-up, including a site visit conducted by the Centers for Disease Control and Prevention, did not identify a clear common source but suggested the possibility of bananas as a food source. Bacillus cereus causes a rapidly progressive, hemorrhagic meningoencephalitis with high mortality among patients with neutropenia. Neuropathologists can play a key role in the detection of outbreaks.

Ophthalmic manifestations of giant cell arteritis

GCA, the most common systemic arteritis, affects medium-sized and larger extradural arteries that have the internal elastic lamina. Involvement of the ophthalmic artery and its branches results in visual loss, which is often complete but is usually painless. Visual loss may be monocular or binocular developing simultaneously or sequentially. Rarely, it stems from occipital lobe infarct that result in homonymous hemianopia, a visual field defect involving the two identical halves (right or left) of the visual fields of both eyes. Visual hallucinations and diplopia are less common. All visual symptoms, including those that are transient, require urgent ophthalmological evaluation and treatment with high-dose glucocorticoids to avoid permanent visual loss.