A case of multiple sclerosis with intractable hiccups and sleep apnea syndrome]

A 48-year-old female with multiple sclerosis (MS) accompanied by intractable hiccups of over one month' duration and the sleep apnea syndrome was reported. This MS patient had been well controlled until September 16, 1991 when she experienced nausea, vomiting and hiccups. The patient was admitted to Kawasaki Medical School Hospital on October 9, 1991. A physical examination revealed intractable hiccups. T1-weighted MRI showed a low and T2-weighted image disclosed a high signal intensity area in the tegmentum of the medulla oblongata. The intractable hiccups and vomiting improved with intravenous high dose methylprednisolone injection therapy. The following day, she complained of insomnia and her family observed severe snoring and apnea during the night. These symptoms and the results of a breathing monitor were compatible with the sleep apnea syndrome. These symptoms disappeared following the administration of amitriptyline. There have been few reports of the combination of intractable hiccups and the sleep apnea syndrome in MS. The MRI findings suggest that the causative lesion of these symptoms is in the tegmentum of the medulla oblongata.     

Clinical analysis of neuromyelitis optica presenting as intractable nausea,vomiting and hiccups

Vomiting and hiccups can be the manifestations of numerous systemic and neurological illnesses. Intractable nausea, vomiting and hiccups (INH) are reported as possible initial manifestations of neuromyelitis optica (NMO), but not correctly identified. Awareness of these atypical presentations is conducive to NMO early diagnosis and proper treatment to prevent further disability. In this paper, 12 NMO were reported, whose intractable vomiting and hiccups were the sole manifestations of the first attack and other attacks involving spinal cord and optic nerves developed later. All the patients were women and serum aquaporin 4 antibody (AQP4-Ab) of 83% patients was positive. MRI of 50% patients showed T2-weighted imaging/fluid attenuated inversion recovery hyperintensity which were longitudinally extensive transverse myelitis or linear signal changes. Sixty-seven percent of patients had medulla lesions, in which dorsomedial and area postrema were involved.     

Intractable vomiting and hiccups as the presenting symptom of neuromyelitis optica

Vomiting and hiccups can be due to peripheral or central causes. Neurological diseases causing vomiting and hiccups are due to lesions of medulla involving area postrema and nucleus tractus solitarius. Neuromyelitis optica (NMO) is one such disease which involves these structures. However refractory vomiting and hiccups as the presenting symptom of NMO is unusual. Here we report a patient with NMO in whom refractory vomiting and hiccups were the sole manifestation of the first attack. Diagnosis can be missed at this stage leading to delay in treatment and further complications. This case demonstrates the importance of considering NMO in any patient presenting with refractory vomiting and hiccups and with local and metabolic causes ruled out and linear medullary lesion on magnetic resonance imaging may indicate the diagnosis even when the classical clinical criteria are not met. Anti NMO antibody testing should be done and if positive appropriate treatment should be initiated to prevent further neurological damage.     

Atypical presentations of neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4) has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks.     

Area postrema syndrome as initial manifestation in neuromyelitis optica spectrum disorder patients: A retrospective study

BackgroundArea postrema syndrome (APS) is recognized as a core feature in neuromyelitis optica (NMO) diagnosis. Isolated APS can occur at NMO onset and frequently results in a delay of diagnosis, along with devastating secondary neurologic deficits. To date, few studies have characterized APS-onset neuromyelitis optica spectrum disorder (APSO-NMOSD).ObjectiveWe aimed to describe the clinical and radiologic features of patients with APSO-NMOSD who are initially misdiagnosed in a cohort of patients from Zhengzhou, China.Materials and methodsWe identified 15 patients who presented with APS as an initial manifestation, based on the 2015 international consensus diagnostic criteria for NMOSD, and reviewed their demographic, clinical, laboratory, and magnetic resonance imaging (MRI) data.ResultFifteen patients (3 men, 12 women) aged 14–50 years old were included in our study. All patients presented with APS that included intractable nausea, vomiting, or hiccups (INVH) as the initial manifestation; many experienced a delay in diagnosis. Serum AQP4 was positive in eleven patients and myelin oligodendrocyte glycoprotein (MOG) in one patient. All patients had a linear medullary lesion or a linear medulla-spinal lesion on sagittal MRI. An “inverted V sign” on axial medulla oblongata images, representing a lesion involving the area postrema, was noted in seven patients in this study.ConclusionsAPS can occur as a sole and initial manifestation of NMOSD, often leading to misdiagnosis in the early process of disease. Identifying patients with an “inverted V” sign and a linear medullary lesion upon MRI examination can help to quickly identify APS patients and avoid further diagnostic delays.     

Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

OBJECTIVE: To assess the evidence for diagnostic tests and therapies for transverse myelitis (TM) and make evidence-based recommendations. METHODS: A review of the published literature from 1966 to March 2009 was performed, with evidence-based classification of relevant articles. Recommendations: Level B recommendations: neuromyelitis optica (NMO)-immunoglobulin G (IgG) antibodies should be considered useful to determine TM cause in patients presenting with clinical acute complete transverse myelitis (ACTM) features. The presence of NMO-IgG antibodies (aquaporin-4-specific antibodies) should be considered useful in determining increased TM recurrence risk. Level C recommendations: in suspected TM, distinction between ACTM or acute partial transverse myelitis may be considered useful to determine TM etiology and risk for relapse (more common with APTM). Age and gender may be considered useful to determine etiology in patients presenting with TM syndrome, with spinal infarcts seen more often in older patients and more female than male patients having TM due to multiple sclerosis (MS). Brain MRI characteristics consistent with those of MS may be considered useful to predict conversion to MS after a first partial TM episode. Longer spinal lesions extending over >3 vertebral segments may be considered useful in determining NMO vs MS. CSF examination for cells and oligoclonal bands may be considered useful to determine the cause of the TM syndrome. Plasma exchange may be considered in patients with TM who fail to improve after corticosteroid treatment. Rituximab may be considered in patients with TM due to NMO to decrease the number of relapses. Level U recommendations: there is insufficient evidence to support or refute the efficacy of other TM therapies or the usefulness of ethnicity to determine the cause of a subacute myelopathy.     

Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two pathologies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentation, laboratory findings (MRI and CSF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. CSF and MRI data were clearly different: oligoclonal bands (OCB) were found in 23% of NMO cases and 88% of MS (P < 0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P < 0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P < 0.001). Clinical outcome was evaluated as more severe in the NMO group (P < 0.001). On the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. Our study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two pathologies but only when MRI data were applied. This finding could have implications for future therapeutic trials.     

Pathologic laughing and intractable hiccups can occur early in multiple sclerosis

Pathologic laughing occurs in approximately 10% of patients with multiple sclerosis (MS), especially when patients have entered the chronic stage. We describe four patients with MS who, at an early stage, developed pathologic laughing associated, in two cases, with intractable hiccups. In two patients, MRI showed an enhanced lesion in the medulla oblongata and the mesencephalon, two regions suspected of being involved in pathologic laughing and intractable hiccups.     

A case of relapsing multiple sclerosis presenting with only autonomic symptoms including orthostatic hypotension, hiccups and vomiting]

A 49-year-old woman, with a two-year-history of multiple screlosis (MS), noticed postural dizziness, intractable hiccups and vomiting. On admission, she had mild quadriparesis, hypesthesia below the C5 level, and a girdle sensation at the T5 and L1 levels. A CSF examination showed slight increases in the protein level (48 mg/dl) and cell count (7/mm3). Brain MRI demonstrated no obvious lesion in the medulla oblongata. The head-up-tilting test showed a decrease in the blood pressure from 105/63 mmHg to 70/55 mmHg. The pulse rate, however, increased from 57/min to 72/min. The cold pressure test also revealed a mild impairement in her blood pressure response. The R-R interval variation (coefficient of variation: CVRR) during normal breathing was 2.58 (normal: > 1.66). The valsalva ratio was 1.84 (normal: 1.4-2.0). The Aschner eye-ball pressure test, the blood pressure response to the injection of epinephrine, and the sweating response to the injection of acetylcholine were all normal. She was thus administered domperidone and chlorpromazine. Only domperidone effectively improved the nausea and vomiting. All symptoms, including orthostatic hypotension, hiccups and vomiting, disappeared about one month after admission. The remission of her symptoms was considered to reflect the natural course of MS. The results of autonomic nervous system function tests and her clinical features suggest that an irritable lesion in the medullary tegmentum, including the nucleus tractus solitarii, most likely caused her symptoms. The above findings indicate that autonomic symptoms, such as orthstatic hypotension, hiccups and vomiting, may sometimes be the only symptoms observed in a relapse of MS.     

Star fruit (Averrhoa carambola) toxic encephalopathy

Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.     

Devic's neuromyelitis optica: a critical review

Devic's neuromyelitis optica (NMO) is an idiopathic inflammatory demyelinating and necrotizing disease characterized by predominant involvement of the optic nerves and spinal cord. In Asian countries relapsing NMO has been known as opticospinal multiple sclerosis. It has long been debated if NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recent studies have shown that NMO has more frequently a relapsing course, and results from attack to aquaporin-4 which is the dominant water channel in the central nervous system, located in foot processes of the astrocytes. Distinctive pathological features of NMO include perivascular deposition of IgG and complement in the perivascular space, granulocyte and eosinophil infiltrates and hyalinization of the vascular walls. These features distinguish NMO from other demyelinating diseases such as MS and acute demyelinating encephalomyelopathy. An IgG-antibody that binds to aquaporin-4, named NMO-IgG has high sensitivity and specificity. Magnetic resonance imaging (MRI) studies have revealed that more frequently there is a long spinal cord lesion that extends through three or more vertebral segments in length. Brain MRI lesions atypical for MS are found in the majority of cases. Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosupressive agents are recommended for prophylaxis of relapses.     

Hypothalamic abnormality in patients with inflammatory demyelinating disorders

Background: Hypothalamic lesions in neuromyelitis optica (NMO) patients might be more specific for NMO than multiple sclerosis (MS). However, this is controversial. Objective: To characterize clinical features of patients with inflammatory demyelinating disorders (IDDs) with visible hypothalamic lesions using magnetic resonance imaging (MRI). Methods: Patients with IDDs (n = 429) were recruited retrospectively. Results: Of 52 patients with hypothalamic images enrolled, 42 were positive for aquaporin-4 (AQP4) antibodies, including 28 patients with NMO, 6 with recurrent transverse myelitis, 3 with recurrent optic neuritis, and 5 with brainstem and brain syndrome. The remaining 10 patients were anti-AQP4-negative, including 3 with MS, 3 with acute disseminated encephalomyelitis, and 4 with other disorders. In the AQP4-positive group, manifestations, including ataxia, intractable hiccup and nausea, syndrome of inappropriate antidiuretic hormone secretion and encephalopathy were more frequent in those with hypothalamic lesions than those without. Cell counts of cerebrospinal fluid in patients with hypothalamic lesions differed from patients without lesions. Brain MRI abnormalities were more frequent in brainstem and hemisphere of the hypothalamic lesion group. Conclusions: Hypothalamic lesions were observed frequently in patients with AQP4 antibodies. Clinical manifestations and paraclinical features in AQP4-positive patients with hypothalamic lesions differed from those without lesions.     

Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.     

Case report Intractable hiccups and syncope in multiple sclerosis

A patient with multiple sclerosis (MS) who developed intractable hiccups and syncope due to a cervical cord lesion is reported. Previous case reports of intractable hiccups occurring in MS have all been located in the medulla oblongata. Our patient is the first case with the responsible lesion in the cervical cord. The pathophysiological mechanism of the syncopal attacks in this case were thought to be same as that of cough syncope.     

A central demyelinating disease with atypical features

There are clinical, laboratory and imaging criteria to distinguish multiple sclerosis (MS) from neuromyelitis optica (NMO) and acute disseminated encephalomyelitis (ADEM). While MS has unknown aetiology, NMO is commonly associated with vasculitis and ADEM is supposed to be parainfectious in origin. In the present study, six patients are described from a group of 67 with a central demyelinating disorder whose clinical presentation did not conform to existing diagnostic criteria for ADEM, NMO or MS. Their clinical, laboratory and imaging characteristics were studied and analysed. Some features suggested a particular diagnosis but some other features favoured another diagnosis. The features included spinal cord involvement in a large vertical segment with cord swelling, optic neuritis, no lesions in the cerebral cortex, paraplegia with urinary retention during the acute phase, no oligoclonal band in cerebrospinal fluid, absence of any evidence of vasculitis, wide time-gap between spinal cord and optic nerve involvement, good recovery from acute phase of disease and a relatively benign course. We conclude that there exists a subpopulation of patients with central demyelinating disease in this region with mixed clinical features. Overall features suggested either a widened clinical spectrum of MS, NMO or ADEM or a possible overlap between them.     

临床孤立综合征转归为视神经脊髓炎的相关因素分析

目的探讨临床孤立综合征(CIS)转归为视神经脊髓炎(NMO)的影响因素。方法收集2004-09-2011-09就诊于作者医院神经内科CIS患者109例。回顾性分析所有患者首次发病时头颅和脊髓MRI特点及临床表现。采用酶联免疫吸附法(ELISA)检测血清水通道蛋白4抗体(AQP4-Ab)水平,另备30份健康者血清作为健康对照组,以高于健康对照组血清AQP4-Ab浓度的均值+3倍标准差者为阳性。结果 (1)随访0.5～7年,中位数为3.0年,四分位数间距为4.6年,转归为NMO 46例,转归为多发性硬化(MS)29例,其余仍是CIS,包括24例脊髓炎,10例视神经炎(ON)。(2)转归为NMO组血清AQP4-Ab水平明显高于MS组、脊髓炎组、ON组和健康对照组(P<0.05)。(3)转归为NMO组AQP4-Ab阳性率为63.03%(29/46),高于转归为MS组的13.79%(4/29)、脊髓炎组的29.17%(7/24)、ON组的20.00%(2/10),差异均有统计学意义(P<0.05)。(4)多因素分析结果提示:AQP4-Ab阳性、NMO颅内典型病灶、脊髓损伤>3个节段、扩展残疾状态量表(EDSS)与CIS转归为NMO有关。结论 AQP4-Ab阳性、NMO颅内典型病灶或者脊髓损伤>3个节段、EDSS评分对预测CIS转归为NMO有临床价值。     

Demyelinating disorder of the central nervous system occurring in black South Africans

OBJECTIVES: To investigate the nature and cause in eight black South African patients of a recurrent (multiphasic), remitting, and relapsing demyelinating disease of the CNS. METHODS: The clinical and laboratory investigations and radiological manifestations of these patients were documented. RESULTS: Each patient had two or more acute attacks of demyelinating disease affecting the CNS. The clinical presentations of the patients were predominantly those of multiphasic neuromyelitis optica (NMO). Brain MRI in these patients showed features consistent with those described for acute disseminated encephalomyelitis (ADEM), as well as lesions that are described in multiple sclerosis. There was involvement of the corpus callosum in addition to typical ADEM lesions. Laboratory investigations excluded all other known causes of multiphasic CNS demyelination. Oligoclonal antibodies were not detected in these patients at any time. The patients were all from a population with a low risk for MS (black South Africans). CONCLUSION: The patients described here represent a new phenotypic expression of a recurrent (multiphasic), steroid sensitive, inflammatory demyelinating disorder of the CNS occurring in black South Africans. The disorder is either a distinct inflammatory demyelinating disorder of the CNS of as yet unknown aetiology, or a varied form of MS (ADEM/NMO) occurring in a population with a low risk (where the genetic trait and environmental risk factors for MS do not exist) for MS.     

Aquaporin-4 autoantibody: a neurogenic cause of anorexia and weight loss

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease often associated with a highly specific autoantibody, aquaporin-4 antibody. Although the classic syndrome involves the optic nerves and spinal cord, aquaporin-4 antibody has been important in defining the true spectrum of NMO, which now includes brain lesions in areas of high aquaporin-4 expression. Brainstem involvement, specifically area postrema involvement in the medulla, has been associated with intractable vomiting in some patients with NMO. We describe a 14-year-old female with positive aquaporin-4 antibody whose clinical course was dominated by severe anorexia with associated weight loss (from 68-41kg; body mass index 25.2-15.6). Magnetic resonance imaging showed lesions in the medulla, pons, and thalami. Although she had asymptomatic radiological longitudinally extensive transverse myelitis, she never had symptoms or signs referable to the spinal cord or the optic nerves. We propose that anorexia and weight loss should be considered part of the NMO spectrum, probably related to area postrema involvement.     

Preferential spinal central gray matter involvement in neuromyelitis optica

Objective To delineate the MRI features that distinguish neuromyelitis optica (NMO) from multiple sclerosis (MS). Methods We compared the distribution of the spinal cord lesions by analyzing 1) lesion area, 2) lesion density (by superimposing the lesions onto the standard sections of the cervical and thoracic cord with appropriate transparencies using computer software), and 3) T1-hypointensity in axial sections of MRI in NMO and MS. Results In NMO, 60–70% of the cervical and thoracic cord MRI lesions occupied more than half of the cord area and mainly involved the central gray matter in the acute stage. In the chronic stage, half or more of the lesions were localized at the central gray matter region. The lesion superimposition analysis also revealed much higher densities in the central gray matter region than in the peripheral white matter regions. Two patients with NMO had T1-hypointense lesions in the central region. In contrast, over 80% of the lesions in MS were localized in the lateral and posterior white matter regions of the cord in the chronic as well as acute stage. Lesion densities were much higher in the lateral and posterior white matter regions than in the central gray matter region. None of the lesions in MS were T1-hypointense. Conclusions These MRI findings strongly suggest a preferential involvement in the spinal central gray matter in NMO which is distinct from MS.     

Devics Neuromyelitis optica Entität oder Variante der Multiplen Sklerose?

Neuromyelitis optica (NMO, or Devic's syndrome) is a rare syndrome characterized by the combination of acute or subacute optic neuritis and transverse myelitis. This strict confinement of lesions together with immunologic parameters such as frequent absence of oligoclonal banding despite increased signs of CSF inflammation suggest that NMO is distinct from multiple sclerosis (MS). Magnetic resonance imaging (MRI) data support NMO and MS as separate entities due to lesion distribution and signal characteristics. This is further supported by epidemiological and genetic evidence associating HLA-DRB1*1501 with disseminated "western" MS in contrast to NMO associated with DRB1*802, DPB1 501, and DPA1 202, the "Asian" type. Most findings suggest a heterogeneous pathogenesis of NMO and, in spite of the distinct localization, rather unspecific immune reactions seem to be involved. As to the frequent relapses of NMO, therapeutic options besides prednisolone are difficult to assess and favor long-term immune suppression or modulation.