Acute motor axonal neuropathy in association with Sjögren syndrome.

Sjögren syndrome (SS) has been known to manifest with neurological complications, most frequently of the peripheral nervous system, and often in advance of xerostomia and xerophthalmia. There has been one case report of a patient with SS presenting with acute motor neuropathy similar to Guillain-Barré syndrome (GBS). We report the case of a patient who developed rapidly fulminant acute motor axonal neuropathy (AMAN) with positive anti-GM1 antibody at high titers in association with serological and pathological evidence of SS without xerostomia or xerophthalmia.

Hypnopompic seizures.

The relationship between epilepsy and sleep is complex and bidirectional. Ictal awakening is probably a common and well-described phenomenon. In this small observational study we describe arousal from sleep as the only, or at least main, manifestation of some epileptic seizures. We coin the term "hypnopompic seizures" to describe this entity. Five patients with intractable epilepsy were monitored by continuous video-electroencephalogram. Four of them had left temporal lobe epilepsy and one patient had generalised epilepsy. Hypnopompic seizures accounted for 30-100% of their seizure types captured during monitoring. All the seizures occurred during stage II sleep and were brief. Hypnopompic seizures are extremely subtle and may be underdiagnosed and underreported. Future larger studies are needed to shed some light on this unique entity and its neuropathophysiology. Epileptologists should be aware of this type of seizure and careful review of electroencephalograms during the transition from sleep to arousal is imperative to capture these seizures. Physicians, patients and families also need to be aware of such a subtle manifestation of seizures. Improved awareness of hypnopompic seizures and subtle seizures, in general, help guide accurate and early diagnosis, thorough monitoring and appropriate management.

Idiopathic transverse myelitis and neuromyelitis optica: clinical profiles, pathophysiology and therapeutic choices.

Transverse myelitis is a focal inflammatory disorder of the spinal cord which may arise due to different etiologies. Transverse myelitis may be idiopathic or related/secondary to other diseases including infections, connective tissue disorders and other autoimmune diseases. It may be also associated with optic neuritis (neuromyelitis optica), which may precede transverse myelitis. In this manuscript we review the pathophysiology of different types of transverse myelitis and neuromyelitis optica and discuss diagnostic criteria for idiopathic transverse myelitis and risk of development of multiple sclerosis after an episode of transverse myelitis. We also discuss treatment options including corticosteroids, immunosuppressives and monoclonal antibodies, plasma exchange and intravenous immunoglobulins.

Isolated central nervous system vasculitis associated with antiribonuclear protein antibody.

We describe the case of a young woman who was referred to a tertiary care center with unexplained subacute progressive encephalopathy preceded by long-standing severe headaches. Her extensive workup was remarkable for abnormal intracranial angiography suggestive of small- and medium-vessel vasculitis, persistently elevated protein in the cerebrospinal fluid and persistently high titers of antiribonuclear protein antibody. The patient showed a modest response to intravenous high-dose steroids. We propose that the patient's neurologic disease is secondary to immune-mediated central nervous system vasculitis, possibly as an initial manifestation of mixed connective tissue disease.

A middle-aged woman with logopenic progressive aphasia as a precursor of Alzheimer's disease: case report and review of the literature.

PRIMARY PROGRESSIVE APHASIA IS A NEURODEGENERATIVE DISORDER THAT WAS RECENTLY CLASSIFIED INTO THREE TYPES: fluent (semantic), nonfluent, and logopenic. The logopenic variant is the least common one and is closely related to Alzheimer's disease in comparison to the other two variants that are closely related to frontotemporal dementia. We report the case of a middle-aged woman who presented to our center with progressive aphasia that was undiagnosed for two years. The patient's neurological evaluation including positron emission tomography is consistent with a logopenic variant of primary progressive aphasia.

CNS intravascular lymphoma: a case report.

Intravascular lymphoma is a rare but well-described entity. The clinical manifestations are heterogeneous. We report a case of a 59-year-old woman who presented initially with syncope followed by subacute cognitive decline that progressed to minimally conscious state. Shortly after the transfer to our tertiary center the patient died. Brain autopsy disclosed the diagnosis of B-cell intravascular lymphoma. We speculate that syncope could be the first manifestation of central nervous system intravascular lymphoma and should be considered in the differential diagnosis of unexplained syncope. In addition, we stress the importance of early brain biopsy in unexplained white matter disease.

Multiple sclerosis and chronic cerebrospinal venous insufficiency: a critical review.

Chronic cerebrospinal venous insufficiency (CCSVI) was recently proposed as a contributing factor in the pathology of multiple sclerosis. This concept has gained remarkable attention, partly because endovascular neurointervention has been suggested as a treatment strategy. This review summarizes available evidence and provides a critical analysis of the published data. Currently, there is inconclusive evidence to support CCSVI as an etiological factor in patients with multiple sclerosis. Endovascular procedures should not be undertaken outside of controlled clinical trials.

The increasing incidence and prevalence of female multiple sclerosis--a critical analysis of potential environmental factors.

Multiple sclerosis (MS) is the most common acquired inflammatory demyelinating disorder of the central nervous system (CNS). Not unlike many inflammatory diseases with a presumed autoimmune pathogenesis, it has been established that there is a female preponderance in prevalence. While in the past it was shown that there are two women for every man with a diagnosis of MS, recent serial cross-sectional assessments provide compelling evidence for an increase of the female to male sex ratio in patients with relapsing-remitting MS over the last decades. An understanding of this phenomenon might provide key insights into the pathogenesis of the disease but also may have implications for health-care strategies and further research efforts. We review possible etiologies for the gender disparity in MS, and we discuss possible underlying causes. We determined that the biologically most plausible explanations for a disproportional increase of MS among women in some population may be the role of vitamin D in MS pathogenesis. Decreased sun exposure may be a critical factor in diminished vitamin D levels in many recent cohort studies. Vitamin D insufficiency or deficiency has been shown to affect T cell differentiation and regulation, which may affect cellular immune responses against autoantigens and pathogens that have been associated with the etiology of MS. Vitamin D also appears to impact B cell activation and differentiation, another cell type that has been implicated in the inflammatory cascade underlying CNS autoimmune disease.

Anti-glutamic Acid decarboxylase antibody-associated ataxia as an extrahepatic autoimmune manifestation of hepatitis C infection: a case report.

Extrahepatic immunological manifestations of hepatitis C virus (HCV) are well described. In addition, antiglutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is well-established entity. However, there have been no reports in the literature of anti-GAD antibody-associated ataxia as an extrahepatic manifestation of HCV infection. We report the case of a young woman with chronic hepatitis C virus and multiple extrahepatic autoimmune diseases including Sjögren syndrome and pernicious anemia who presented with subacute midline cerebellar syndrome and was found to have positive antiglutamic acid decarboxylase (GAD) antibody in the serum and cerebrospinal fluid. An extensive diagnostic workup to rule out neoplastic growths was negative, suggesting the diagnosis of nonparaneoplastic antiglutamic acid decarboxylase antibody-associated cerebellar ataxia as an additional extrahepatic manifestation of hepatitis C virus infection. The patient failed to respond to high-dose steroids and intravenous immunoglobulin. Treatment with the monoclonal antibody rituximab stabilized the disease. We postulate that anti-GAD associated ataxia could be an extrahepatic manifestation of HCV infection.

No cerebral or cervical venous insufficiency in US veterans with multiple sclerosis.

OBJECTIVE: To determine if chronic cerebral venous insufficiency exists in patients with multiple sclerosis (MS) using ultrasonography and 4-dimensional color Doppler ultrasonography examination and unverified criteria proposed by Zamboni et al. DESIGN: Patients with MS and clinically isolated syndrome were matched by age and sex with subjects with migraine or no neurological disease. All subjects underwent gray-scale, color, and spectral Doppler ultrasonography examination of the internal jugular veins (IJVs), vertebral veins, and deep cerebral veins for stenosis, absence of signal, and reflux. SETTING: Academic MS center. PATIENTS: All patients with MS fulfilled revised McDonald criteria for the diagnosis of MS. Patients with clinically isolated syndrome exhibited a typical transient focal neurological deficit and had magnetic resonance imaging lesions typical of MS. Control subjects were recruited from the VA migraine clinic or staff. MAIN OUTCOME MEASURES: Five parameters of venous outflow used by Zamboni et al were examined: (1) IJV or vertebral vein reflux, (2) deep cerebral vein reflux, (3) IJV stenosis, (4) absence of flow in IJVs or vertebral veins, and (5) change in cross-sectional area of the IJV with postural change. RESULTS: There was no significant difference in the number and type of venous outflow abnormalities in patients with MS compared with controls. CONCLUSION: This study does not support the theory that chronic cerebral venous insufficiency exists in MS.

Multiple sclerosis in the elderly patient.

Multiple sclerosis (MS) is an acquired inflammatory demyelinating disease of the CNS that is typically diagnosed in the second or third decade of life. It is generally believed that over the last few decades the life expectancy of patients with adult onset MS (AOMS) has approached that of the general population as a result of better medical and nursing care. Thus, an increasing number of MS patients are entering or have reached senescence. A second group of elderly patients with MS that may be very different in terms of disease pathogenesis are patients with late onset MS (LOMS). The diagnosis in LOMS patients can be challenging because of a large number of age-associated MS differential diagnoses, atypical presentations, a low index of suspicion and the lack of diagnostic criteria specific to this age group. Also, specific problems these patients encounter have only recently become a focus of attention. Changes in renal and hepatic function with age, in addition to the coexistence of medical co-morbidities, require special attention in the management of elderly patients with MS. In this review we outline the characteristics of senescent AOMS and LOMS patients. In addition, we discuss therapeutic strategies in elderly patients with MS based on our knowledge of immunosenescence and age-associated characteristics of this disorder. Given the overall aging of the population, focusing on these two patient groups appears highly relevant.

Immunopathogenesis of multiple sclerosis: new insights and therapeutic implications.

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disorder of the CNS. The etiology of MS remains unknown. However, it is well established that immune dysregulation plays a critical role in the neuropathogenesis of this disorder. In this review, we discuss the current hypotheses concerning the complex cellular and molecular interactions involved in the immunopathogenesis of MS. Although CD4 T lymphocytes have long been considered the critical cellular factor in the immunopathology of MS, the role of other cell types has also recently been investigated. It appears that the spatial distribution of CD4 and CD8 cells in MS lesions is distinct. Yet another T-lymphocyte subset, γ/δ T cells, can be detected in very early MS lesions. The prevalent dogma suggests that CD4 helper T (TH) type 1 cells release cytokines and inflammatory mediators that cause tissue damage, while CD4 TH2 cells might be involved in modulation of these effects. However, a mounting body of evidence suggests that additional T-cell subsets, including TH17 cells, CD8 effector T cells, and CD4 CD25 regulatory T cells, also affect disease activity. In addition, clinical and paraclinical data are accumulating on the prominent role of B lymphocytes and other antigen-presenting cells in MS neuropathogenesis. Given these observations, new therapeutic interventions for MS will need to focus on resetting multiple components of the immune system.

Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis.

The laboratory evaluation of cerebrospinal fluid (CSF) has been routinely employed as a diagnostic test in the diagnosis of neuroimmunological disorders such as multiple sclerosis (MS). Recently, CSF analyses in MS have garnered renewed interest as a tool for monitoring disease activity and prognosis. With the identification of patients that are very early in their disease course, namely patients with a radiologically isolated (RIS) or a clinically isolated syndrome (CIS), the true value of these evaluations has yet to be fully explored. Ultimately, the hope is that biomarkers within this compartment will be identified that will identify etiologic factors of MS and other inflammatory disorders of the central nervous system. In this review we discuss the history of CSF diagnostic tests and the most recent methodological advances. We also outline the potentially important diagnostic role and possible limitations of these tests.

Translational research in neurology and neuroscience 2010: multiple sclerosis.

Over the past 2 decades, enormous progress has been made with regard to pharmacotherapies for patients with multiple sclerosis. There is perhaps no other subspecialty in neurology in which more agents have been approved that substantially alter the clinical course of a disabling disorder. Many of the pharmaceuticals that are currently approved, in clinical trials, or in preclinical development were initially evaluated in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis. Two Food and Drug Administration-approved agents (glatiramer acetate and natalizumab) were developed using the experimental autoimmune encephalomyelitis model. This model has served clinician-scientists for many decades to enable understanding the inflammatory cascade that underlies clinical disease activity and disease surrogate markers detected in patients.

Cyclophosphamide in multiple sclerosis: scientific rationale, history and novel treatment paradigms.

For patients with relapsing-remitting multiple sclerosis (RRMS), there are currently six approved medications that have been shown to alter the natural course of the disease. The approved medications include three beta interferon formulations, glatiramer acetate, natalizumab and mitoxantrone. Treating aggressive forms of RRMS and progressive disease forms of MS still presents a great challenge to neurologists. Intense immunosuppression has long been thought to be the only feasible therapeutic option. In patients with progressive forms of MS, lymphoid tissues have been detected in the central nervous system (CNS) that may play a critical role in perpetuating local inflammation. Agents that are currently approved for patients with MS have no or very limited bioavailability in the brain and spinal cord. In contrast, cyclophosphamide (CYC), an alkylating agent, penetrates the blood-brain barrier and CNS parenchyma well. However, while CYC has been used in clinical trials and off-label in clinical practice in patients with MS for over three decades, data on its efficacy in very heterogeneous groups of study patients have been conflicting. New myeloablative treatment paradigms with CYC may provide a therapeutic option in patients that do not respond to other agents. In this article we review the scientific rationale that led to the initial clinical trials with CYC. We will also outline the safety, tolerability and efficacy of CYC and provide neurologists with guidelines for its use in patients with MS and other inflammatory disorders of the CNS, including neuromyelitis optica (NMO). Finally, an outlook into relatively novel treatment approaches is provided.

Optic neuritis presenting with amaurosis fugax.

Optic neuritis usually presents with rapid and gradual loss of vision that is either complete or incomplete, and typically associated with retro-orbital pain. To our knowledge there have been no documented reports of optic neuritis presenting with multiple episodes of amaurosis fugax, the sudden and transient loss of vision lasting seconds to minutes. We report here the case of a young woman with a possible diagnosis of demyelinating left optic neuritis that presented solely with multiple episodes of brief and transient sudden loss of vision. Ophthalmological exams were normal between episodes of vision loss. The patient's magnetic resonance imaging of the brain showed a subtle enhancement of the left optic nerve along with multiple periventricular lesions, highly suggestive of a demyelinating disease. The frequent episodes of visual loss resolved completely with high dose parenteral steroids. Neurologists and other clinicians should be aware of this unusual presentation of optic neuritis as treatment modalities differ greatly from other causes of amaurosis fugax.