Central nervous system fungal infections in tropics

Fungal infections of the central nervous system range from chronic indolent forms to acute fulminant forms causing significant morbidity and mortality. They often show atypical and variable neuroradiologic findings because of the absence of typical inflammatory response. The neuroradiologist must have high degree of suspicion in immunocompromised patients regarding the possibility of central nervous system fungal infections and keep in mind the appearances of various fungi even when immune response is intact. Next is to identify the pattern of involvement whether hematogenous or direct sinonasal and then make a well-informed speculation regarding the type of the pathogen based on the clinical features and imaging appearance.     

Fungal infections of the central nervous system in HIV-negative patients: Experience from a tertiary referral center of South India

Objective:

To describe the clinical, radiological, and cerebrovascular fluid (CSF) findings and the outcome of microbiologically or histopathologically proven fungal infections of the central nervous system (CNS) in HIV-negative patients.

Methodology and Results:

We identified definite cases of CNS mycosis by screening the medical records of our institute for the period 2000–2008. The clinical and imaging details and the outcome were abstracted from the medical records and entered in a structured proforma. There were 12 patients with CNS mycosis (i.e., 2.7% of all CNS infections treated in this hospital); six (50%) had cryptococcal infection, three (25%) had mucormycosis, and two had unclassified fungal infection. Four (33%) of them had diabetes as a predisposing factor. The common presentations were meningoencephalitis (58%) and polycranial neuritis (41%). Magnetic resonance imaging revealed hydrocephalus in 41% and meningeal enhancement in 25%, as well as some unusual findings such as subdural hematoma in the bulbocervical region, carpeting lesion of the base of the skull, and enhancing lesion in the cerebellopontine angle. The CSF showed pleocytosis (66%), hypoglycorrhachia (83%), and elevated protein levels (100%). The diagnosis was confirmed by meningocortical biopsy (in three cases), paranasal sinus biopsy (in four cases), CSF culture (in three cases), India ink preparation (in four cases), or by cryptococcal polysaccharide antigen test (in three cases). Out of the ten patients for whom follow-up details were available, six patients recovered with antifungal medications (amphotericin B, 1 mg/kg/day for the minimum period of 6 weeks) and/or surgical treatment. Four patients expired (only one of them had received antifungal therapy).

Conclusions:

Most patients with CNS mycosis recover with appropriate therapy, but the diagnosis and management of these rare infections remains a challenge to clinicians.     

Plasmapheresis in neurological disorders: Experience from a tertiary care hospital in South India

Background:

Therapeutic plasma exchange (PE) or plasmapheresis is the treatment of choice in many neurological disorders. Even though it is safe in experienced hands, there is a major concern about its safety among physicians.

Objectives:

To analyze our experience with 230 patients who underwent PE for various neurological disorders.

Materials and Methods:

Retrospective review of PE procedures done during a period of 48 months, from July 2007 to June 2011 in a tertiary care teaching hospital in South India. Indications, clinical results and technical factors are discussed.

Results:

The main indication for PE was GBS (203 patients; 88.3%). Age of patients ranged from 14-65 (mean = 42.3 years). The most common complications were paraesthesias and/or cramps (36.1%) and hypotension (32.2%). Four pregnant patients who underwent PE had good recovery with one intrauterine death. There was no mortality.

Conclusion:

The analysis of 240 cases of PE done in our department shows that the procedure is safe, with only minimal procedure related complications and no mortality.     

Pediatric tumors of the central nervous system: a retrospective study of 1,043 cases from a tertiary care center in South India

Objective  

The objective of this study is to describe the age, sex, location, and histopathology of pediatric tumors of the central nervous system diagnosed at a tertiary care center in South India.     

Neurological associations in auditory neuropathy spectrum disorder: Results from a tertiary hospital in South India

Aims:

To find out the prevalence and types of neurological abnormalities associated in auditory neuropathy spectrum disorder in a large tertiary referral center.

Settings and Design:

A prospective clinical study was conducted on all patients diagnosed with auditory neuropathy spectrum disorder in the ear, nose, and throat (ENT) and neurology departments during a 17-month period. Patients with neurological abnormalities on history and examination were further assessed by a neurologist to determine the type of disorder present.

Results:

The frequency of auditory neuropathy spectrum disorder was 1.12%. Sixty percent were found to have neurological involvement. This included cerebral palsy in children, peripheral neuropathy (PN), spinocerebellar ataxia, hereditary motor-sensory neuropathy, spastic paresis, and ponto-bulbar palsy. Neurological lesions did not present simultaneously with hearing loss in most patients. Sixty-six percent of patients with auditory neuropathy spectrum disorder were born of consanguineous marriages.

Conclusions:

There is a high prevalence of neurological lesions in auditory neuropathy spectrum disorder which has to be kept in mind while evaluating such patients. Follow-up and counselling regarding the appearance of neuropathies is therefore important in such patients. A hereditary etiology is indicated in a majority of cases of auditory neuropathy spectrum disorder.     

我国人类免疫缺陷病毒和梅毒螺旋体感染中枢神经系统研究进展

获得性免疫缺陷综合征(亦称艾滋病)和梅毒在全球范围内广泛流行,严重危害国家公共卫生安全。我国对人类免疫缺陷病毒(HIV)相关中枢神经系统损害及神经梅毒的研究日益增多。本文检索目前国内学者发表的HIV和梅毒螺旋体感染中枢神经系统的相关文献,总结其流行病学特征、发病机制、临床特点、诊断与治疗策略,以为临床诊断与治疗提供新的思路。     

Role of cytokines and chemokines in prion infections of the central nervous system

Prion infections of the central nervous system (CNS) are characterised by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrP(res)-activated glia cells may contribute directly or indirectly to the disease development by enhancement and generalisation of the gliosis and via cytotoxicity for neurons. However, the actual role of prion-induced glia activation and subsequent cytokine/chemokine secretion in disease development is still far from clear. In the present work, we review our present knowledge concerning the functional biology of cytokines and chemokines in prion infections of the CNS.     

Central nervous system immune reconstitution inflammatory syndrome in AIDS: experience of a Mexican neurological centre

Background

Highly active antiretroviral therapy (HAART) restores the inflammatory immune response in AIDS patients and it may unmask previous subclinical infections or paradoxically exacerbate symptoms of opportunistic infections. Up to 25% of patients receiving HAART develop immune reconstitution inflammatory syndrome (IRIS). We describe six patients with IRIS central nervous system (CNSIRIS) manifestations emphasizing the relevance of CSF cultures and neuroimaging in early diagnosis and management.

Methods

Patients with CNSIRIS were identified among hospitalized HIV-infected patients that started HAART from January 2002 through December 2007 at a referral neurological center in Mexico.

Results

One-hundred and forty-two HIV-infected patients with neurological signs were hospitalized, 64 of which had received HAART, and six (9.3%) developed CNSIRIS. Five patients were male. Two cases of tuberculosis, two of cryptococcosis, one of brain toxoplasmosis, and one possible PML case were found. IRIS onset occurred within 12 weeks of HAART in five patients. Anti-infective therapy was continued. In one case, HAART was temporarily suspended. In long-term follow-up the clinical condition improved in all patients.

Conclusions

CNSIRIS associated to opportunistic infections appeared in 9% of patients receiving HAART. Interestingly, no cases of malignancy or neoplasm IRIS-related were found. Frequent clinical assessment and neuroimaging studies supported diagnosis and treatment. Risk factors were similar to those found in other series.     

Central nervous system toxoplasmosis in acquired immunodeficiency syndrome: An emerging disease in India.

With the incidence of patients infected with human immuno-deficiency virus (HIV) increasing in India, the central nervous system (CNS) manifestations of the disease will be seen more frequently. The CNS may be primarily afflicted by the virus or by opportunistic infections and neoplasms secondary to the immune suppression caused by the virus. In India, although mycobacterium tuberculosis has been reported to be the most common opportunistic infection, toxoplasmosis may become as common owing to the ubiquitous nature of the protozoan. Since an empirical trial of medical therapy without histopathological diagnosis is recommended, the true incidence of this condition may remain under estimated. The role of ancillary tests such as radiology and serology in the initial diagnosis of this condition remain crucial. This report highlights two patients who were diagnosed to have acquired immuno-deficiency syndrome (AIDS) only after the biopsy of the intracranial lesion was reported as toxoplasmosis. Presently all patients for elective neurosurgery are tested for HIV antigen. The management protocol to be followed in a known patient with AIDS presenting with CNS symptoms is discussed in detail. The value of ancillary tests is also reviewed.     

Varied presentations of moyamoya disease in a tertiary care hospital of north-east India

Introduction:

Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs), anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs), accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India.

Objectives:

To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India.

Material and Methods:

Relevant investigations were done to rule out other causes of moyamoya syndrome.

Results:

We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA) in addition to stenosis of bilateral ICAs, ACAs and MCAs.

Conclusion:

Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients.     

The association between central nervous system (CNS) infections and epilepsy: Epidemiological approaches and microbiological and epileptological perspectives

The causal association between central nervous system (CNS) infections and epilepsy is predictable but poorly documented due to constraints in epidemiological, epileptological, and microbiologic methods. The large number of CNS infections with varied geographic distributions means that epidemiological studies in many different regions are required in order to establish their association with epilepsy. Whenever infectious diseases occur in the community, the majority of the infected cases are either asymptomatic or develop only mild symptoms. Those with neurological involvement and hence at risk of developing epilepsy constitute the tip of the iceberg. Furthermore, there is no one-to-one relationship between surrogate markers of infection used in epidemiological studies (e.g., seropositivity or brain imaging abnormalities) and neurological involvement (and hence epilepsy). As a result, there are individuals in the community who have no neurological symptoms but may either be seropositive or demonstrate imaging abnormalities compatible with the neurological infectious disorder and conversely, those who have seizures (or epilepsy) but may be seronegative. Relevant to the epidemiological study of seizures and epilepsy in relation to CNS infections is the classification of seizures as provoked and unprovoked . Accordingly, seizures that occur during the active stage of infection are considered provoked and those that occur later are unprovoked . Finally, with the burden of infections being concentrated in the less-developed countries, epidemiological studies are required to be carried out in these locations, which present logistic, financial and technical barriers for them to be accomplished.     

Review: Central nervous system involvement in mitochondrial disease

Mitochondrial respiratory chain defects are an important cause of inherited disorders affecting approximately 1 in 5000 people in the UK population. Collectively these disorders are termed ‘mitochondrial diseases’ and they result from either mitochondrial DNA mutations or defects in nuclear DNA. Although they are frequently multisystem disorders, neurological deficits are particularly common, wide‐ranging and disabling for patients. This review details the manifold neurological impairments associated with mitochondrial disease, and describes the efforts to understand how they arise and progressively worsen in patients with mitochondrial disease. We describe advances in our understanding of disease pathogenesis through detailed neuropathological studies and how this has spurred the development of cellular and animal models of disease. We underscore the importance of continued clinical, molecular genetic, neuropathological and animal model studies to fully characterize mitochondrial diseases and understand mechanisms of neurodegeneration. These studies are instrumental for the next phase of mitochondrial research that has a particular emphasis on finding novel ways to treat mitochondrial disease to improve patient care and quality of life.     

Central nervous system infection in a murine retrovirus-induced immunodeficiency syndrome

Astrocyte-enriched primary glial cultures (AGC) from C57BL/6 mice were found to be highly susceptible to infection with the replication competent components of LP-BM5, consisting of the ecotropic and mink cell focus-inducing (MCF) helper murine leukemia viruses (MuLVs). The presence in infected AGC of defective LP-BM5 MuLV genome, a critical component for induction of the disease referred to as murine AIDS, was confirmed by Southern blot hybridization using a probe reactive with the p12 gag sequence of the 4.9 kb defective genome. Electron microscopic studies demonstrated C-type retrovirus particles in both astrocytes and microglial cells. In vivo studies demonstrated that the ecotropic MuLVs and the defective genome could be detected within AGC obtained form either 14-day-old mice following intraperitoneal inoculation or 7-day-old mice following intracranial inoculation. These findings suggest that: (1) the central nervous system (CNS) infection is present at an early stage in murine AIDS, (2) both astrocytes and microglial cells are possible CNS targets in which helper MuLVs replicate, and (3) these cells can harbor the defective genome that is a critical component for disease induction.     

Neurons of the ascidian larval nervous system in Ciona intestinalis: I. Central nervous system

The tadpole larva of ascidians, basal living relatives of vertebrates, has a chordate body plan. The CNS has many homologies with that of vertebrates yet only about 100 neurons. These few, possibly fixed in number and composition, nevertheless govern a diverse repertoire of behaviors. To elucidate the circuits of the CNS first requires that we recognize each neuron type, for which we used electroporation to transfect precleavage embryos with a plasmid containing green fluorescent protein (GFP) driven by the promoter of the synaptotagmin gene. Hatched larvae were fixed and GFP 3-D reconstructions of confocal image stacks compiled into images of 31 whole or partial larvae, either with many GFP-labelled neurons or with few, each clearly visible. Neuron counts in the sensory vesicle (SV) and visceral ganglion (VG) indicated that between 75% (SV) and 69% (VG) of previously reported numbers of neurons were transfected. Based on their position, shape, and projections, the following neurons were identified in the SV: a prominent eminens neuron, possibly with direct input from papillar neurons, a large ventroposterior interneuron, photoreceptors of the ocellus, and putative antenna cells of the otolith. In the VG, we identified at least four subtypes of motor neuron, including an ovoid cell that may innervate distal tail muscle cells and contrapelo cells with ascending projections, unique among VG neurons. The caudal nerve cord contained the first reported neurons, the somata of planate neurons. These neurons are the first identified types, and will be used to construct a map of the nervous system for this model basal chordate.     

Central nervous system involvement in hereditary neuropathy with liability to pressure palsies: description of a large family with this association

OBJECTIVE: To describe a large family with hereditary neuropathy with liability to pressure palsies associated with central nervous system demyelination. DESIGN: We examined the 18 members of a pedigree. Genetic analysis was performed on 15 subjects, standard nerve conduction studies on 10 subjects, and brain magnetic resonance imaging studies on 8 subjects. RESULTS: Hereditary neuropathy with liability to pressure palsies was confirmed in 9 patients of the pedigree. Brain magnetic resonance imaging findings showed multiple areas of demyelination in 6 of 6 affected members and were normal in 2 of 2 healthy relatives. Magnetic resonance imaging abnormalities were predominantly located in the subcortical frontal white matter. All patients had acute and recurrent nerve palsies, while clinical features of central nervous system involvement were not a characteristic of this pedigree. CONCLUSIONS: We demonstrate that this association, previously reported in sporadic cases, is not coincidental. Therefore, patients with hereditary neuropathy with liability to pressure palsies can present central nervous system white matter lesions, and the role of the PMP22 (peripheral myelin protein 22) gene deletion in the central nervous system should be further studied.