Brainstem Syndrome Research Articles

Crossed brainstem syndrome revealing bleeding brainstem cavernous malformation: an illustrative case

BackgroundSince the nineteenth century, a great variety of crossed brainstem syndromes (CBS) have been described in the medical literature. A CBS typically combines ipsilateral cranial nerves deficits to contralateral long tracts involvement such as hemiparesis or hemianesthesia. Classical CBS seem in fact not to be so clear-cut entities with up to 20% of patients showing different or unnamed combinations of crossed symptoms. In terms of etiologies, acute brainstem infarction predominates but CBS secondary to hemorrhage, neoplasm, abscess, and demyelination have been described. The aim of this study was to assess the proportion of CBS caused by a bleeding episode arising from a brainstem cavernous malformation (BCM) reported in the literature.Case presentationWe present the case of a typical Foville syndrome in a 65-year-old man that was caused by a pontine BCM with extralesional bleeding. Following the first bleeding episode, a conservative management was decided but the patient had eventually to be operated on soon after the second bleeding event.DiscussionA literature review was conducted focusing on the five most common CBS (Benedikt, Weber, Foville, Millard-Gubler, Wallenberg) on Medline database from inception to 2020. According to the literature, hemorrhagic BCM account for approximately 7 % of CBS. Microsurgical excision may be indicated after the second bleeding episode but needs to be carefully weighted up against the risks of the surgical procedure and openly discussed with the patient.ConclusionsIn the setting of a CBS, neuroimaging work-up may not infrequently reveal a BCM requiring complex multidisciplinary team management including neurosurgical advice.

Paraneoplastic neuromyelitis optica spectrum disorders: a case series.

Aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSD) are rare idiopathic autoimmune diseases, presenting with optic neuritis (ON), longitudinally extensive transverse myelitis (LETM), and brainstem syndromes and a prevalence range between 0.5 and 4/100,000. Only 3% to 25% of NMOSD have been described as a paraneoplastic (PN) syndrome (PNNMOSD). Both idiopathic NMOSD (INMOSD) and PNNMOSD cases mostly affect females, but PNNMOSD usually presents with a spinal cord or brainstem involvement in elderly patients. Few cases of both malignancies (for the majority breast or lung cancer) and benign tumors (monoclonal gammopathy) were previously reported. Currently, there is no consensus on treatment approach for PNNMOSD (only surgical removal or surgery combined with chronic immunosuppression). Here, we present a series of three newly diagnosed PNNMOSD cases, who differ from each other for demographic and clinical features, tumor association, long-term treatment, and outcome. We propose that a PN etiology should be considered always whenever a new diagnosis of NMOSD is made, not only in patients over 50years old or in spinal cord/brainstem lesions presentations. Our findings add to existing evidence and raise awareness on PNNMOSD. We enhance the importance for the clinicians of recognizing tumor symptoms and signs whenever a NMOSD is newly diagnosed.

Editorial Highlights on Multiple Cranial Neuropathy

Patients presenting with multiple cranial neuropathies are not uncommon in neurologic clinical practice. The evaluation of these patients can often be overwhelming due to the vast and complicated etiologies as well as the potential for devastating neurologic outcomes. Dysfunction of the cranial nerves can occur anywhere in their course from intrinsic brainstem dysfunction to their peripheral courses. The focus of this review will be on the extramedullary causes of multiple cranial neuropathies as discussion of the brainstem syndromes is more relevant when considering intrinsic disorders of the brainstem. The goals are to provide the reader with an overview of those extramedullary conditions that have a predilection for causing multiple cranial nerve palsies. In turn, this will serve to provide a practical and systematic approach to allow for a more targeted diagnostic evaluation of this, often cumbersome, presentation.

Relapsing neuromyelitis optica spectrum disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disorder of the central nervous system. Relapsing NMOSD (RNMOSD) is being reported frequently, leading to severe and permanent relapse related disability.Aims and Objectives: To study the clinical profile and imaging features of the NMOSD cases at the index time and addressing the long-term clinical spectrum of relapsing type of NMOSD who presented to the tertiary care hospital. Materials and Methods: All patients who attended the King George Hospital, Visakhapatnam and fulfilled the diagnostic criteria of NMOSD were studied for the epidemiological details, type of clinical spectrum on relapses, imaging features and treatment prescribed, and were studied between April, 2011 and March, 2018.Results: Total diagnosed cases were 28, out of which relapsing type were seen in 11 patients and all tested positive for antibodies. Female to male ratio is 3:1, and in RNMOSD group all were females. Most common clinical presentation was myelitis followed by optic neuritis. Noted clinical spectrum in the RNMOSD was unusual presentations like one each patient of Area-Postrema syndrome, diencephalic syndrome, cerebral syndrome, acute brainstem syndrome, and frequent relapses within a month in two. Five cases had also associated systemic autoimmune disorders.Conclusion: RNMOSD is very rapidly evolving disease, affecting primarily young women with wide spectrum of neurological presentations and also other non-neurological systemic features. Early diagnosis and aggressive immune therapy in the early phase might be warranted in NMOSD for relapse prevention and improving the quality of life.

Emerging Targeted Therapies for Neuromyelitis Optica Spectrum Disorders.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder of the central nervous system that typically presents with recurrent episodes of optic neuritis, longitudinally extensive myelitis, brainstem, diencephalic, and cerebral syndromes. Up to 80% of NMOSD patients have a circulating pathogenic autoantibody that targets the water channel aquaporin-4 (AQP4-IgG). The discovery of AQP4-IgG transformed our understanding of the pathogenesis of the disease and its possible treatment targets. Monoclonal antibodies targeting terminal complement (eculizumab), CD19 (inebilizumab), and the interleukin-6 receptor (satralizumab) have demonstrated efficacy in NMOSD attack prevention in recent phase 3 trials and have gained subsequent regulatory approval in the USA and other countries. We aim to review the evidence supporting the efficacy of these new drugs.

Myelin oligodendrocyte glycoprotein-antibody-associated disorder: a new inflammatory CNS demyelinating disorder.

Myelin oligodendrocyte glycoprotein (MOG) is an oligodendrocytopathy resulting in demyelination. We aimed to determine the frequency of MOG-associated disorders (MOGAD), its various clinical phenotypes, and imaging characteristics. All patients with MOGAD were included. Description of the various clinical phenotypes, investigation profile, therapeutic response, differences between pediatric and adult-onset neurological disorders, determination of poor prognostic factors was done. The study population consisted of 93 (M:F = 45:48) (Pediatric:40, Adult-onset:47, Late-onset:7) patients with a median age of 21years. Among the 263 demyelinating episodes; 45.8% were optic neuritis (ON), 22.8% were myelopathy, 17.1% were brainstem, 7.6% were acute demyelinating encephalomyelitis(ADEM), 4.2% were opticomyelopathy and 2.3% with cerebral manifestations. There was exclusive vomiting in 24.7% prior to onset of clinical syndrome, none of them had area postrema involvement. ADEM was exclusively seen in pediatric patients. Poor prognostic indicators included: (i) incomplete recovery from an acute attack, (b) brainstem syndrome, (c) ADEM with incomplete recovery, (d) MRI suggestive of leukodystrophy pattern, (e) severe ON, (f) ADEMON. The Spectrum of MOG-associated disorders is wider affecting the brain (grey and white matter) and the meninges. There are various clinical phenotypes and MRI patterns, recognition of which may help in the determination of therapeutic strategies, and long-term prognosis.

Multicentric clinical and epidemiological comparison of neuromyelitis optica spectrum disorder with multiple sclerosis from India

BackgroundIn India, Neuromyelitis optica spectrum disorders (NMOSD) can often be misdiagnosed as multiple sclerosis (MS) leading to wrong or delayed treatment. Although diagnostic criteria exist it is important to flag certain highlights in the phenotype by direct comparison which will prompt investigation in the right direction. The aim was to identify distinguishing features, especially differences in disability status and frequency of the optico-spinal syndrome. MethodsThis study was designed as a multicentric, hospital based, ambispective, observational study of patients with primary demyelination due to either NMOSD or MS. Various variables were collected using a data extraction proforma and were compared using statistical means. ResultsA total of 212 patients, 166 (78.3%) with MS and 46 (21.7%) with NMOSD, were included from six different cities across India. The male to female ratio was 1:1.3 in MS group and 1:2.3 in NMOSD group. Significant differences on logistic regression included: patients with NMOSD were more disabled despite having a shorter duration of illness with a high progression index (EDSS/ duration of disease in years) of 5.99 vs 0.74 respectively (p = 0.02); in subset of relapsing patients relapsing optico-spinal syndrome (optic neuritis with myelitis) was more common in NMOSD (39.1% vs 0.8%); presence of at least one T2 lesion in the last available MRI brain (78.6% vs 39.1%) and presence of at least one gadolinium enhancing lesion in brain MRI documented during course of illness (30.2% vs 8.7%) was more in MS patients. If the patient with demyelination had a progression index of ≥ 0.39, the Likelihood Ratio (LR) of having NMOSD was 1.32 (95% CI 1.06–1.64), the sensitivity was 0.74 and specificity 0.44. Other notable variables significant on univariate but not on multivariate analysis were: other autoimmune diseases were present more in the NMOSD group (13% vs 2.4%); proportion of patients who had only school education (up to class 12) but not higher were more in NMOSD (67.4% vs 38.5%); the most common clinical presentation in MS patients was either a brainstem or cerebral syndrome (41% vs 21.8%) while it was isolated myelitis in NMOSD patients (37% vs 19.3%). Other findings included: optic neuritis as a presenting feature was common and present in similar proportions in both the groups (around 37%); 50% (23/46) of NMOSD and around 30% (50/166) of MS patients had a single clinical episode during the course of their illness and in the relapsing patients, mean no of relapses (around 2.7) and ARR (MS 0.38, NMOSD 0.54) were similar. Secondary progressive MS was diagnosed in 4.8% (8/166) and primary progressive MS was diagnosed in 3.7% (6/166). ConclusionIndex of suspicion for NMOSD should be high in a patient if: the course is relatively short; disability is out of proportion and progression index is ≥0.39 or the patient has had recurrent optico-spinal relapses. It is important to distinguish early in the course NMOSD from MS as timely specific treatment may prevent future disability.

Cognitive impairment in NMOSD-More questions than answers.

IntroductionNeuromyelitis optica spectrum disorder (NMOSD) is a type of central nervous system antibody‐mediated disease which affects mainly optic nerves and spinal cord, but may also present with acute brainstem syndrome, acute diencephalic syndrome, and cerebral syndrome with typical brain lesions. One of the most disabling symptoms, diagnosed in 29%–67% of cases, is cognitive dysfunction, with such processes as memory, processing speed, executive function, attention, and verbal fluency being predominantly affected. However, description of cognition in NMOSD patients is still a relatively new area of research.MethodsA systematic MEDLINE search was performed to retrieve all studies that investigated cognitive impairment and its clinical correlates in patients with NMOSD.ResultsWe summarize the current knowledge on cognitive impairment profile, neuropsychological tests used to examine NMOSD patients, clinical and demographical variables affecting cognition, and magnetic resonance imaging correlates. We provide a comparison of cognitive profile of patients with multiple sclerosis and NMOSD.ConclusionPatients with NMOSD are at significant risk of cognitive deficits. However, the knowledge of cognitive symptoms in NMOSD and potential modifying interventions is still scarce. Further accumulation of clinical data may facilitate effective therapeutic interventions.

Using the Lateral Pontine Safe Entry Zone for Resection of Deep-Seated Cavernous Malformations in the Lateral Pons: 2-Dimensional Operative Video.

The retrosigmoid approach is one of the main approaches used in the surgical management of pontine cavernous malformations. It definitely provides a lateral route to large central lesions but also makes possible resection of some ventral lesions as an alternative to the petrosal approaches. However, when these vascular malformations do not emerge on surface, one of the safe corridors delimited by the origin of the trigeminal nerve and the seventh-eight cranial nerve complex can be used.1-5 Baghai et al2 described the lateral pontine safe entry zone in 1982, as an alternative to approaches through the floor of the fourth ventricle when performing tumor biopsies. They advocated a small neurotomy performed right between the emergence of the trigeminal nerve and the facial-vestibulocochlear cranial nerves complex. Accurate image guidance, intraoperative cranial nerve monitoring, and comprehensive anatomical knowledge are critical for this approach.4,5 Knowing the natural history of a brainstem cavernous malformation after bleeding,6 we sought to demonstrate in this video: (1) the use of the retrosigmoid craniotomy in lateral decubitus for resection of deep-seated pontine cavernous malformations; (2) the wide opening of arachnoid membranes and dissection of the superior petrosal vein complex to improve surgical freedom and prevent use of fixed cerebellar retraction; and (3) the opening of the petrosal fissure and exposure of the lateral pontine zone for gross total resection of a cavernous malformation in a 19-yr-old female with a classical crossed brainstem syndrome. She had full neurological recovery after 3 mo of follow-up. The patient consented in full to the surgical procedure and publication of the video and manuscript.

CASE REPORT-NEUROMYELITIS OPTICA/ DEVIC'S DISEASE: A RARE DISEASE

Neuromyelitis Optica spectrum disorder or Devic’s disease are autoimmune diseases that manifest clinically with 6 core symptoms, which include acute optic neuritis, transverse longitudinal segment myelitis, and acute brainstem syndrome.{1}Neuromyelitis optica is characterized by attacks of optic neuritis and longitudinally extensive transverse myelitis. It is often confused with multiple sclerosis. Early discrimination between NMO and MS is important because the two diseases have different natural histories and treatment regimens. Despite the absence of a definitive therapeutic strategy for NMO syndrome, methylprednisolone pulse therapy is recommended in acute phase. Treatment strategies in relapse phases are aimed at preventing relapses, and increasing evidences show a better clinical response of immunosuppressive therapy than immunomodulating therapy. We report a case of NMSOD in a patient of age 55 , with transverse myelopathy as the initial manifestation. The patient presented with acute gait disturbance and hypoesthesia in right lower limb since 10 days . After thorough physical examination and various lab investigations and imaging, the patient received high dose methylprednisolone. The patient’s serum was positive for anti-AQP4 antibodies .During the course of treatment , patient again presented with complaint of blurred vision in the ER after 1 year. Diagnosis of NMSOD was established. After combining methylprednisolone and immunosuppressant therapy , the patient’s medical condition was stable and relapses were prevented.

Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide.

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes. Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease. AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis. For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults. Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis. Double-seronegative disease requires further research and clarification. Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide. One relevant finding is the varying prevalence observed in different racial groups. Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of <1/million population. Among East Asians, the prevalence is higher, at ~3.5/100,000 population, while the prevalence in Blacks may be up to 10/100,000 population. For MOG-antibody disease, hospital-based studies largely do not observe any significant racial preponderance so far. This disorder comprises a significant proportion of NMOSD cases that are AQP4-antibody-seronegative. A recent Dutch nationwide study reported the annual incidence of MOG-antibody disease as 1.6/million population (adult: 1.3/million, children: 3.1/million). Clinical and radiological differences between AQP4-antibody and MOG-antibody associated diseases have led to interest in the revisions of NMOSD definition and expanded stratification based on detection of a specific autoantibody biomarker. More population-based studies in different geographical regions and racial groups will be useful to further inform the prevalence and incidence of NMOSD and their antibody-specific subgroups. Accessibility to AQP4-antibody and MOG-antibody testing, which is limited in many centers, is a challenge to overcome. Environmental and genetic studies will be useful accompaniments to identify other potential pathogenetic factors and specific biomarkers in NMOSD.

Epidemiology of Pediatric NMOSD in Germany and Austria.

Background: Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory demyelinating disorders of the central nervous system mainly characterized by recurrent episodes of uni- or bilateral optic neuritis (ON), transverse myelitis (TM) and brainstem syndromes (BS). The majority of adult patients has serum antibodies directed against the water channel protein aquaporin 4 (AQP4-abs). In pediatric patients, AQP4-abs are less, while antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) are more frequently detectable than in adults. Some children with NMOSD have neither AQP4- nor MOG-ab (double-seronegative).Objective: Evaluation of epidemiological data regarding incidence and prevalence of pediatric NMOSD in Germany and Austria.Methods: We recruited pediatric NMOSD patients between 1 March 2017 and 28 February 2019 with five different tools: (1) ESPED (Surveillance Unit for Rare Pediatric Disorders in Germany), (2) ESNEK (Surveillance for Rare Neurological Disorders during Childhood), (3) pediatric neurology working group within the Austrian Society of Pediatrics and Adolescent Medicine, (4) BIOMARKER Study and (5) NEMOS (Neuromyelitis optica Study Group). We requested data regarding clinical symptoms, antibody status, therapy regimen and response via a standardized questionnaire.Results: During the 2-year recruitment period, 46 (both incidental and prevalent) patients with a suspected diagnosis of NMOSD were brought to our attention. Twenty-two of these patients did not fulfill the inclusion criteria. Of the remaining 24 children, 22 had a median age at onset of 11 (range 3–17) years and 16/22 were female (72.7%) (no data in two patients). Sixteen of 24 patients were AQP4-ab positive (67%), 4/24 MOG-ab positive (16.7%), three children were double-seronegative and in one patient no antibody testing was done. We calculated an incidence rate of 0.022 per 100,000 person-years for Germany, while there was no incidental case in Austria during the recruitment period. The prevalence rate was 0.147 and 0.267 per 100,000 persons in Germany and Austria, respectively.Conclusion: Pediatric NMOSD, with and without associated antibodies, are very rare even considering the different limitations of our study. An unexpected finding was that a considerable proportion of patients was tested neither for AQP4- nor MOG-abs during diagnostic work-up, which should prompt to establish and disseminate appropriate guidelines.

Diagnostic features of initial demyelinating events associated with serum MOG-IgG

BackgroundMyelin oligodendrocyte glycoprotein (MOG)-IgG associated disorders are increasingly recognized as a distinct disease entity. However, diagnostic sensitivity and specificity of serum MOG-IgG as well as recommendations for testing are still debated. Materials and methodsBetween October 2015 and July 2017 we tested serum MOG-IgG in 91 adult patients (49 females) with a demyelinating event (DE) not fulfilling 2010 McDonald criteria for MS at sampling, negative for neuromyelitis optica (NMO)-IgG and followed-up for at least 12 months. We assessed the sensitivity and specificity of a live-cell MOG-IgG assay for each final diagnosis at last follow-up, for the 2018 international recommendations for MOG-IgG testing, and for other combinations of clinical and laboratory characteristics. ResultsClinical presentations included acute myelitis (n = 48), optic neuritis (n = 36), multifocal encephalomyelitis (n = 4), and brainstem syndrome (n = 3). Twenty-four patients were MOG-IgG positive. Sensitivity and specificity of MOG-IgG test applied to the 2018 international recommendations were 28.4% and 86.7%, while they were 42.1% and 88.6% when applied to DE of unclear aetiology as defined above with two or more among: 1_no periventricular and juxtacortical MS-like lesions on brain MRI; 2_longitudinally extensive MRI optic nerve lesion; 3_no CSF-restricted oligoclonal bands; 4_CSF protein > 50 mg/dl. ConclusionsSimplified requirements compared to those currently proposed for MOG-IgG testing could facilitate the applicability of the assay in the diagnosis of adults with DEs of unclear aetiology.

“Nine Syndrome”: A Rare Neuroophthalmological Syndrome Associated with HIV Vasculopathy

AbstractThere are many named brainstem syndromic variants of medullary infarcts among which “eight-and-a-half” syndrome is a rare condition that involves ipsilateral abducens nucleus or paramedian pontine reticular formation, ipsilateral medial longitudinal fasciculus, and adjacent facial colliculus/facial nerve. Here, we describe a new variant of brainstem syndrome, which includes the clinical features of “eight-and-a-half syndrome” with associated hemiparesis. This patient is a known case of HIV illness since 6 years on antiretroviral therapy, presented with features of “Nine” syndrome.

Anti-myelin oligodendrocyte glycoprotein antibody associated disease spectrum – A north Indian tertiary care centre experience and review of literature

IntroductionMOG antibody associated disease is a relatively new disorder for which the full clinical spectrum is being described and the literature is evolving. The current study outlines the observations on a cohort of patients diagnosed with this clinical entity. MethodsThis is a retrospective review of prospectively followed up patients with MOG antibody positive neurological illness. Case records of patients following up in neuroimmunology clinic of All India Institute of Medical Sciences(AIIMS), New Delhi from January 2007 to July 2019 were reviewed for MOG antibody positivity and those patients with positive antibody result were included in this study. FindingsA total of 20 patients were tested positive for MOG-IgG antibody. 75% were females. Median (Range) age was 30.5 years (8-58). Median disease duration was 22 months (1–139). Most common symptom at presentation was decrease in vision (unilateral or bilateral) (80%). Most common syndrome at onset was unilateral optic neuritis (ON) (40%) followed by bilateral ON (35%), transverse myelitis (TM)(15%), ON plus TM (5%) and cerebral syndrome (5%). Median number of demyelinating episodes per person was 2.5. Out of 29 affected eyes, 26 had good outcome. Out of 7 patients with motor disability, 5 patients had good outcome. ConclusionMOG antibody associated disease presents predominantly as recurrent ON, but may also present as an opticospinal, cerebral or brainstem syndrome and recurrent myelitis. Many of the patients had relapses, but had good outcomes with treatment.

The Multiple Cranial Nerve Palsies: A Prospective Observational Study.

Neurological presentation with isolated multiple cranial nerve palsies is common and its diverse causes include infectious, neoplastic, and inflammatory pathologies. The aetiological spectrum may depend upon geographical regions. We undertook this study to explore clinical spectrum and aetiological profile of multiple cranial nerve palsies. This hospital-based prospective observational study was conducted from August 2015 to August 2017. All the consecutive patients of multiple cranial palsies presenting to the neurology department were included in the studies. Primary objectives were to define anatomical syndromes/cranial nerve combinations and to establish aetiology. Secondary objectives were to study associated factors. The multiple cranial nerve palsy was defined as involvement of two or more non-homologous nerves. Patients of neuromuscular junction disorders, anterior horn cell disorders, myopathies, brain stem syndromes were excluded. All patients underwent structured protocol of clinical evaluation, investigations and few specialized investigations in accordance with clinical suspicion to establish the diagnosis. Fifty-four patients with a mean age of 39.9 ± 14.2 years were included. Commonest cranial nerve involved was the abducens (75.9%) among all nerve combinations. The cavernous sinus syndrome (37%), orbital apex syndrome (22.2%) and jugular foramen syndrome (11.1%) were the most frequent anatomical patterns. Infections (40.7%) were the commonest aetiology followed by neoplastic and idiopathic in four patients. Cavernous sinus syndrome was the commonest anatomical syndrome of multiple cranial nerve palsies and infections were the commonest cause in this study.

Myelin Oligodendrocyte Glycoprotein (MOG) Antibody-Associated CNS Demyelination: Clinical Spectrum and Comparison with Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorder.

The clinical phenotypes of myelin oligodendrocyte glycoprotein (MOG) antibody disease, its disease course, and treatment are poorly understood and much work needs to be done towards this. To characterize the clinico-radiologic spectrum and treatment outcomes of MOG antibody disease and differentiate it from aquaporin-4 (AQP-4) antibody positive neuromyelitis optica spectrum disorders (NMO-SD). A single-center, observational study from Western India during 2017-2019, of 48 patients with either MOG antibody positive (21 patients) or AQP-4 antibody positive (27 patients) central nervous system demyelination. MOG antibody group had median age 32.2 years, no gender bias, median disease duration 40 months, relapses in 9 patients (43%), and median 2.5 (1-16) episodes per patient. Onset phenotypes included isolated bilateral optic neuritis (ON) (43%), isolated unilateral ON (19%), acute brainstem syndrome (19%), simultaneous ON with myelitis (9%), isolated myelitis (5%), and acute disseminated encephalomyelitis optic neuritis (ADEM-ON) (5%). Characteristic neuroimaging abnormalities were anterior segment longitudinally extensive ON, upper brainstem, and thoracic cord involvement (both short and long segment lesions). Most patients (86%) responded well to steroids, only 3/21 required rescue immunotherapy. In total, 6 out of 46 eyes affected developed permanent visual disability, while one patient had motor disability. The features differentiating MOG from AQP-4 antibody group were: no female predilection, preferential optic nerve involvement, characteristic neuroimaging abnormalities, and favorable therapeutic response and outcome. MOG disease commonly presents as severe ON, myelitis, acute brainstem syndrome, ADEM or their combinations. Early identification, treatment, and maintenance immunosuppression are necessary. It can easily be differentiated from NMO-SD using clinico-radiological features and therapeutic response.

What do we currently know about the clinically isolated syndrome suggestive of multiple sclerosis? An update.

Multiple sclerosis (MS) is a chronic, demyelinating, not fully understood disease of the central nervous system. The first demyelinating clinical episode is called clinically isolated syndrome (CIS) suggestive of MS. Although the most common manifestations of CIS are long tracts dysfunction and unilateral optic neuritis, it can also include isolated brainstem syndromes, cerebellar involvement, and polysymptomatic clinical image. Recently, the frequency of CIS diagnosis has decreased due to the more sensitive and less specific 2017 McDonald criteria compared with the revisions from 2010. Not all patients with CIS develop MS. The risk of conversion can be estimated based on many predictive factors including epidemiological, ethnical, clinical, biochemical, radiological, immunogenetic, and other markers. The management of CIS is nowadays widely discussed among clinicians and neuroscientists. To date, interferons, glatiramer acetate, teriflunomide, cladribine, and some other agents have been evaluated in randomized, placebo-controlled, double-blind studies relying on large groups of patients with the first demyelinating event. All of these drugs were shown to have beneficial effects in patients with CIS and might be used routinely in the future. The goal of this article is to explore the most relevant topics regarding CIS as well as to provide the most recent information in the field. The review presents CIS definition, classification, clinical image, predictive factors, and management. What is more, this is one of very few reviews summarizing the topic in the light of the 2017 McDonald criteria.

Concomitant abducens and facial nerve palsies: A rare presentation in anti-aquaporin-4 antibody-positive neuromyelitis optica

Over the past decade, the discovery of disease-specific aquaporin-4 antibodies has led to a better understanding of the diverse spectrum of disorders that are associated with neuromyelitis optica. Brainstem manifestations have been increasingly recognized in this disease. However, multiple cranial nerve palsies as an initial presentation of neuromyelitis optica are uncommon. We report a rare case of anti-aquaporin-4 antibody-positive neuromyelitis optica that presented with unilateral abducens and facial nerve palsies. Notably, this case did not involve the optic nerve or the spinal cord. Diagnosing neuromyelitis optica that presents as an isolated acute brainstem syndrome is challenging, but the outcome may be devastating if the diagnosis is delayed.

Nothnagel Syndrome: A rare case of Ischemic Brain Stem Syndrome

‘Nothnagel Syndrome' is a brainstem syndrome which is often underdiagnosed by the physicians due to rarity of the disease and complex clinical presentation. We present a case of brainstem midbrain syndrome caused by ischemic stroke. The male hypertensive diabetic patient presented with sudden onset of diplopia, ptosis and gait imbalance. Right-sidedgaze palsy with nystagmus and ataxic gait were the clinical findings. Brain imaging (MRI and DWI) showed high signal intensity at upper midbrain. The patient was finally diagnosed as ischemic stroke in the brainstem called Nothnagel syndrome. Up to now, there was no case reported as Nothnagel Syndrome due to ischemic stroke.&#x0D; J MEDICINE JAN 2020; 21 (1) : 62-64