Chronic Meningitis: Simplifying a Diagnostic Challenge

Chronic meningitis can be a diagnostic dilemma for even the most experienced clinician. Many times, the differential diagnosis is broad and encompasses autoimmune, neoplastic, and infectious etiologies. This review will focus on a general approach to chronic meningitis to simplify the diagnostic challenges many clinicians face. The article will also review the most common etiologies of chronic meningitis in some detail including clinical presentation, diagnostic testing, treatment, and outcomes. By using a case-based approach, we will focus on the key elements of clinical presentation and laboratory analysis that will yield the most rapid and accurate diagnosis in these complicated cases.     

Chronic meningitis

Chronic meningitis is a syndrome commonly defined by the presence of continuously persistent meningeal inflammation for at least 4 weeks. Presenting neurologic features are often nonspecific, and the list of differential diagnoses is broad. Despite the development of modern molecular diagnostic methods, establishing a specific cause may challenge the acumen of the treating neurologist with clues to the diagnosis residing outside the nervous system and requiring focused investigation. This review discusses selected etiologies illustrating issues in diagnosis and etiologic categories to be considered in the evaluation of this challenging syndrome.     

Spinal Cord Stimulation Has Comparable Efficacy in Common Pain Etiologies

Objectives. The probability of success with spinal cord stimulation (SCS) depends largely on appropriate patient selection. Here, we have assessed the predictive value of pain etiology as it relates to pain relief with SCS as part of a prospective multicenter clinical trial. Methods. Sixty‐five subjects with chronic and intractable pain tested an epidural SCS system. Subjects reported pain ratings (visual analog scale) with stimulation off and stimulation on at scheduled follow‐up visits for up to 18 months after activation of the system. Visual analog scale scores were averaged and stratified by dominant pain etiologies, comprising failed back surgery syndrome, complex regional pain syndrome, and a subgroup of subjects with miscellaneous other pain etiologies. Results. More than 70% of subjects in each subgroup had successful outcomes during the temporary trial period and similar percentages of subjects from each etiology subgroup subsequently went on to permanent implantation. After permanent implantation, all subgroups reported more than 50% pain relief, on average, at each follow‐up time point. No predictive value of pain etiology was observed. Conclusions. Spinal cord stimulation is an effective therapy for neuropathic pain arising from a variety of causes. Failed back surgery syndrome, complex regional pain syndrome, and pain of other etiologies responded equally well to SCS.     

Study of CT and etiology In 11B cases of eoute headache without hemlplegla

objectal To study the relation between CT and etiology of acute headache without hemiplegia. Methods 118 cases of acute headache without hemiplegia were studied with CT scan. The patients with normal CT were diagnosed with lumbar punc -tura or diagnostic standard for establishing disease. Results The first three etiologies were cerebrovescular disease (65 cases, 55%), migraine (25 cases, 21%), meningitis and encephalitis (19 cases, 155. 9%). 53% of patients with subarachnoid hemorrhage(SAH) was diagnosed in CT unnormal group, and 12.4% of patients with Sall was showed by lumbar puncture in CT normal group(P＜0. 001). CT was normal in 18% of patients with a definite SAH(7/39). The positive rates of intracranial infection in CT normal group(by lumbar puncture) was reearkably higher than in CT unnormal group (18/58 versus 2/60, p＜0.005), Conolusion CT is more sensitive to intracranial hemorrhage, tumor and infarction. SAH of a negative Ctscan is not rare. CT is far inferior to lumbar puncture in meningitis or encephalitis.     

Tuberculous meningitis presenting with nonconvulsive status epilepticus

Nonconvulsive status epilepticus (NCSE) is an enduring epileptic condition characterized by alteration in consciousness and continuous ictal discharges on the EEG. Various etiologies have been reported. We describe the case of a 66-year-old woman with altered mental status who was diagnosed with NCSE. A workup to explain the etiology revealed tuberculous meningitis (TBM) with increased cerebrospinal fluid protein and positive tuberculous DNA polymerase chain reaction and interferon-γ assay tests. She was treated according to the status epilepticus protocol with a four-drug anti-tuberculosis regimen to which she responded. TBM is a serious disease with insidious presentation and still constitutes a diagnostic challenge with its various presentations. Among the many presentations of tuberculosis, clinicians should consider NCSE.     

Isolated central nervous system histoplasmosis in an immunocompetent patient: 53-month hiatus to diagnosis and treatment

Chronic meningitis may result from a wide range of etiologies, both infectious and noninfectious, and is often diagnostically challenging. In most series, tuberculosis remains the most common recognized cause. Of the fungal diseases resulting in chronic meningitis,Cryptococcus is the most common. When untreated, the infectious meningitides typically exhibit an inexorably progressive course with high morbidity and mortality. We report a patient with chronic meningitis due toHistoplasma capsulatum who exhibited a remarkably benign course despite being untreated for the disorder for more than 4 years.     

Atraumatic nonaneurysmal sulcal subarachnoid hemorrhages: a diagnostic workup based on a case series

Introduction: Atraumatic and nonaneurysmal sulcal subarachnoid hemorrhage (sSAH) is a rare type of cerebrovascular disease with various etiologies previously reported in small case reports. In this study, we propose to analyze clinical presentations, imaging patterns and etiologies in a large case series of such patients in order to propose a diagnostic workup. Methods: We retrospectively analyzed clinical and radiological data of consecutive patients with a diagnosis of atraumatic and nonaneurysmal sSAH, admitted to our institution between 2008 and 2011. All patients had both computed tomography (CT) and magnetic resonance imaging (MRI) as a part of their initial evaluation. Results: 30 patients (18 women and 12 men, mean age: 60 years) were identified. The main clinical symptoms at presentation were focal and transient neurological deficit (n = 22) and thunderclap headache (n = 10). Four patients had progressive headache and 4 other had partial or generalized epileptic seizures. MRI abnormalities associated with sSAH were prior hemorrhages, microbleeds, severe leukoencephalopathy and hemosiderosis suggesting cerebral amyloid angiopathy (CAA; n = 9), vasogenic edema in parieto-occipital areas compatible with a posterior reversible encephalopathy syndrome (PRES; n = 3), cortical venous thrombosis (n = 2) and concomitant acute cortical stroke (n = 3). Other underlying causes of sSAH, not diagnosed on MRI, were reversible cerebral vasoconstriction syndrome (RCVS) based on clinical criteria and conventional angiography (n = 4), angiitis diagnosed by skin biopsy (n = 1), vascular malformation diagnosed on CT and digital subtraction angiographies (n = 3), and overanticoagulation (n = 1). Four cases remained unresolved. Conclusion: This study confirmed that sSAH is a rare condition related to a wide spectrum of etiologies. Combination of brain MRI and magnetic resonance angiography and eventually digital subtraction angiography allowed the identification of an underlying etiology for 87% of patients. CAA, RCVS and PRES represented more than 50% of the etiological mechanisms. Among older patients, sSAH was mainly related to CAA while in younger patients, RCVS represented the most frequent etiology.     

Aseptic meningitis and viral myelitis

Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.     

Neuroimaging in the definition and organization of the epilepsies: we're not there yet

Neuroimaging significantly affects the diagnosis and treatment of patients with patients. Despite its importance, magnetic resonance imaging (MRI) has been marginally incorporated into concepts used to define epilepsy etiologies by the International League Against Epilepsy (ILAE) Classification Commission. We propose that Structural etiology be defined as positive neuroimaging abnormalities likely causing the seizures. This would contrast with Genetic and Unknown etiologies, where imaging shows no overt structural abnormality that explains the seizures. It is further recommended that Structural and Metabolic be separated into individual categories, as the outcomes and therapies are different. It is advocated that Structural etiology be subdivided into subgroups based on MRI and surgical syndromes. With this approach, the ILAE should acknowledge that both MRI and electroencephalography (EEG) are necessary diagnostic tools in the classification of epilepsy syndromes and etiologies in the modern era. Promoting the use of neuroimaging into concepts that determine terminology will promote the notion that epilepsy classification should consider structural etiology of the seizures, along with the frequency of the most common epilepsy syndromes, and prognosis for spontaneous and treated remission and cure.     

Cerebrospinal fluid formula in patients with central nervous system infection

Knowledge of the CSF formula is clinically useful and at times critical in the analysis of a number of diagnostic problems presented by patients with CNS infections. The decision to withhold antimicrobial therapy in the patient with an acute meningitis syndrome, when viral etiology is suspected, is justified in the presence of a polymorphonuclear cellular reaction provided the CSF glucose is greater than 45 mg per dl and the protein less than 130 mg per dl. Patients who fail to improve clinically should be retapped in 8 to 12 hours. A persisting PMN reaction or the combination of a PMN pleocytosis and hypoglycorrachia virtually rules out viral infection and, in the face of negative routine cultures, requires a diligent search for focal parameningeal suppuration and consideration of CNS tuberculosis and fungal infection. Careful re-evaluation of the patient emphasizing factors such as duration of illness and potential sites of parameningeal suppuration will be useful in guiding further diagnostic studies. Head CT scanning including views of the sphenoid sinuses may be especially helpful in this regard.     

Assessment of physical etiologies for mood and anxiety disorders in structured diagnostic interviews

BACKGROUND: Structured diagnostic inter- views include items that evaluate physical etiologies for mood and anxiety disorders. The objective of this article was to assess the impact of such items. METHOD: A mental health survey in Canada collected data from n = 36,984 household residents. The lifetime prevalence of mood and anxiety disorders was calculated with and without exclusions due to physical causes. RESULTS: Approximately 10% of subjects with a lifetime depressive disorder reported that all of their episodes were due to one or more physical cause. Many of the reported etiologies were implausible given the DSM-IV requirement that the disturbance be a "direct physiological consequence" of the physical cause. The results were similar for manic episodes and anxiety disorders. CONCLUSIONS: Structured diagnostic interviews assess physical etiologies in ways that are subject to inconsistency and inaccuracy. Physical etiology items may bias estimates by introducing etiological opinions into the assessment of disorder frequency.     

Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study.

OBJECTIVE--To test the hypotheses that patients exposed to viral meningitis would be at an increased risk of developing chronic fatigue syndrome and would have an excess of neurological symptoms and physical impairment. METHODS--Eighty three patients were followed up 6-24 months after viral meningitis and a postal questionnaire was used to compare outcome with 76 controls who had had non-enteroviral, non-CNS viral infections. RESULTS--For the 159 patients and controls the prevalence of chronic fatigue syndrome was 12.6%, a rate higher than previously reported from primary care attenders, suggesting that moderate to severe viral infections may play a part in the aetiology of some fatigue states. Those with a history of meningitis showed a slight, non-significant increase in prevalence of chronic fatigue syndrome (OR 1.4; 95% CI 0.5-3.6) which disappeared when logistic regression and analysis was used to correct for age, sex, and duration of follow up (OR 1.0; 95% CI 0.3-2.8). Controls showed marginally higher psychiatric morbidity measured on the general health questionnaire-12 (adjusted OR 0.6; 95% CI 0.3-1.3) Both groups had similar rates of neurological symptoms and physical impairment. The best predictor of chronic fatigue was a prolonged duration time of off work after the illness (OR 4.93, 95% CI 1.3-18.8). The best predictor of severe chronic fatigue syndrome diagnosed by Center for Disease Control criteria was past psychiatric illness (OR 7.82, 95% CI 1.8-34.3). Duration of viral illness, as defined by days in hospital, did not predict chronic fatigue syndrome. CONCLUSIONS--(1) The prevalence of chronic fatigue syndrome is higher than expected for the range of viral illnesses examined; (2) enteroviral infection is unlikely to be a specific risk factor for its development; (3) onset of chronic fatigue syndrome after a viral infection is predicted by psychiatric morbidity and prolonged convalescence, rather than by the severity of the viral illness itself.     

TEMPOROMANDIBULAR JOINT PAIN-DYSFUNCTION SYNDROME: A RARE CAUSE OF HEADACHES IN ADOLESCENTS

The temporomandibular joint pain-dysfunction syndrome has received little attention in the literature on pediatric neurology. Five adolescents with this syndrome are reported, all of whom complained initially of headaches. In all cases the headaches were either continuous or daily and all patients had tenderness of the muscles of mastication and restricted or deviant jaw-opening. The literature is reviewed, and etiology, diagnosis and treatment are discussed. It is concluded that this is a rare but distinct syndrome which can cause headaches in adolescents, appears to have multiple etiologies and should be treated conservatively.     

Cerebrospinal fluid in infection of the central nervous system by yeasts of the genus Candida: analysis of 11 cases

This study is based on the analysis of 44 cerebrospinal fluid (CSF) samples from 11 patients with central nervous system (CNS) Candida infection. Risk factors for CNS fungal infection were present in all patients. Five had a chronic meningitis syndrome; two had acquired immunodeficiency syndrome (AIDS); two had cranial trauma followed by chronic meningities; one had intravascular disseminated coagulation syndrome and sepsis; and one had systemic candidiasis after kidney transplant. Etiological diagnosis was made in all by the CSF examination. Nine cases had positive CSF culture for Candida. Two patients presented the yeast in the direct examination, and one of them had reagent complement fixation test for Candida in three successive samples of CSF. Changes found in the CSF composition are discussed in order to evaluate the inflammatory response to CNS infection by Candida.     

非外伤性皮质凸面蛛网膜下腔出血237例汇集分析

目的探讨非外伤性大脑皮质凸面蛛网膜下腔出血(cSAH)的临床特征,以提高对该病的认识。方法以PubMed和"中国生物医学文献数据库"为主要检索数据库,对2004至2014年发表的中、英文文献26篇中237例CSAH的临床特征进行汇集分析,内容包括病因、临床表现、影像学特征、治疗及预后。结果 cSAH各年龄段均有发病,绝大多数急性起病。脑淀粉样血管病、可逆性脑血管收缩综合征、脑静脉血栓形成、颈内动脉狭窄/闭塞、可逆性后部脑病综合征占全部病因66.67%。常见症状为不同程度的头痛、类似短暂性脑缺血发作的神经功能缺损症状、局限性神经功能缺损以及癫发作。头颅CT阳性检出率87.91%,主要表现大脑皮质凸面条索状出血。大多数cSAH患者预后良好,再出血发生率低。结论 cSAH是蛛网膜下腔出血(SAH)的少见类型,其病因、临床表现及影像学特点与动脉瘤破裂导致SAH不同。对于初次发病的cSAH,要进行全面的脑血管筛查。     

SUDEP, suspected positional airway obstruction, and hypoventilation in postictal coma

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with chronic uncontrolled epilepsy. Despite intense interest in SUDEP from the medical and scientific communities in recent years, its etiologies are still largely unresolved. A 35-year-old woman had SUDEP after having a generalized seizure in the prone position. The cause of her death was likely asphyxia from the convergence of postictal coma and suspected positional airway obstruction and hypoventilation, rather than the commonly suspected periictal cardiac arrhythmia or central apnea. SUDEP may share a similar etiology with sudden infant death syndrome (SIDS) and is likely preventable, at least in a proportion of cases.     

Chronic intestinal pseudo-obstruction in adults: A practical guide to identify patient subgroups that are suitable for more specific treatments

Chronic intestinal pseudo-obstruction is a rare and heterogeneous syndrome characterized by recurrent symptoms of intestinal obstruction with radiological features of dilated small or large intestine with air/fluid levels in the absence of any mechanical occlusive lesion. Several diseases may be associated with chronic intestinal pseudo-obstruction and in these cases, the prognosis and treatment are related to the underlying disease. Also, in its “primary or idiopathic” form, two subgroups of patients should be determined as they require a more specific therapeutic approach: patients whose chronic intestinal pseudo-obstruction is due to sporadic autoimmune/inflammatory mechanisms and patients whose neuromuscular changes are genetically determined. In a context of a widely heterogeneous adult population presenting chronic intestinal pseudo-obstruction, this review aims to summarize a practical diagnostic workup for identifying definite subgroups of patients who might benefit from more specific treatments, based on the etiology of their underlying condition.     

Multiple ring enhancing brain lesions on computed tomography: an Indian perspective

BACKGROUND: Multiple enhancing computed tomography (CT) brain lesions are common neuroimaging abnormalities in India. Several published case reports suggest that multiple enhancing lesions of the brain can occur with a wide variety of infective and non-infective etiologies. METHODS: In this prospective follow up study, 110 consecutive patients with two or more than two enhancing brain lesions were subjected to a clinical evaluation and a battery of common investigative tests. RESULTS: Infective pathologies were the most common etiology for multiple enhancing lesions of the brain. Tuberculosis was the commonest infective pathology, followed by neurocysticercosis. Neoplastic diseases were common non-infective causes. In majority, brain lesions were metastatic manifestation of a systemic neoplastic disorder. Lung carcinoma was the commonest primary malignancy. One patient each had multiple brain abscesses, Behcet's syndrome and systemic lupus erythematosus. Among 4 human immunodeficiency virus-infected patients, one had toxoplasmosis and two patients were diagnosed to have cryptococcal meningitis. In 45 patients, after initial work up, etiological diagnosis could not be ascertained. These undiagnosed patients were empirically treated with antituberculous drugs and corticosteroids. Six undiagnosed patients showed pulmonary metastasis on repeat X-ray chest. In 10 patients CT lesions completely disappeared. In 5 patients number of CT lesions decreased. Six patients died. However, in majority of the undiagnosed patients follow up CT scans of brain remained unaltered. CONCLUSION: A large number of infectious and non-infectious diseases can cause multiple enhancing lesions of the brain. The work up of these patients should include clinical evaluation, imaging and a battery of laboratory tests. The specific diagnosis may remain a challenge in several cases.     

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development

BackgroundEpileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome.MethodsThe etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups.ResultsThe etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups.ConclusionsElectrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence.     

De novo cryptogenic refractory multifocal febrile status epilepticus in the young adult: a review of six cases

BACKGROUND: Status epilepticus (SE) is a common neurological emergency. In around 10 percent, the etiology of SE is not clear, i.e. cryptogenic SE. AIM: To describe six young adult patients with de novo cryptogenic multifocal febrile SE with poor outcome. METHODS: Retrospective chart review. RESULTS: We describe six patients who presented with de novo SE. All were young adults with an unremarkable previous medical history. In all except one, the family history for epilepsy was negative. All had a febrile illness in the week preceding SE. Investigations were unable to reveal the underlying etiology. SE proved refractory to conventional antiepileptic drug treatment (AED) and anesthesia was required to control seizures. Seizures during SE or ensuing epilepsy were multifocal. Brain pathology in four patients was normal in two and showed changes secondary to seizures in two. Outcome was poor in all cases: one patient died during the course of SE, another patient remained with severe mental and physical disability as well as refractory epileptic seizures, the other four developed refractory multifocal epilepsy. One of these patients died a sudden unexpected death in epilepsy (SUDEP) and one drowned during a seizure. CONCLUSIONS: Six patients were reviewed who presented with de novo cryptogenic multifocal refractory febrile SE. The possible etiologies are discussed. Based on the similarities in these cases, a distinct refractory SE syndrome might be assumed. Further prospective studies will, however, be required to validate this hypothesis as well as to elucidate its etiology and optimize treatment.