Etiopathology, Clinical and Imaging Characteristics of Border Zone Strokes.

Introduction: A border zone infarct (BI) is defined as an infarction that is localized to watersheds or border zones in the brain. BI is further classified into cortical border zone infarct (CBZ) and internal border zone infarct (IBZ). This study was conducted to explore the clinical and radiological characteristics of BI. Materials and Method: The study was conducted on eligible 400 acute ischemic stroke patients out of which 52 BI patients (diagnosed by the radiologist on DWI MRI images), patients >18 yrs of age were selected and divided into two groups of IBZ and CBZ infarct patients. The degree of intracranial and extracranial stenosis and characteristics on clinical presentation were assessed. The data were collected and analyzed using SPSS version 20.0 software at significance level p-value <0.05. Results: 25% and 75% of CBZ and IBZ patients, respectively, had history of presyncope or syncope before stroke. On vascular evaluation, 3.9% and 51.9% were in MCA and ICA stenosis group, respectively. Evidence of cardio embolism was found in 17.3% of patients. 53.3% of CBZ and 53.8% of IBZ patients were in ICA stenosis group, and 6.7% of CBZ and 7.7% of IBZ patients were in MCA stenosis group, with a statistically insignificant relation (p-value >0.05). Conclusion: Association of BI with events causing hypotension or hypovolemia is well-established in our study, association of BI with large vessel atherosclerosis is common, and its contribution to CBZ and IBZ seems to be equal.

Isolated Discitis in Melioidosis: An Unknown Presentation and a Microbiological Challenge.

Burkholderia pseudomallei causes Whitmore's disease or melioidosis which is endemic in many South Asian countries including India. This gram-negative bacterium is frequently found in the moist soil and agricultural workers get infected most commonly. Most of the infections are asymptomatic and have a wide spectrum of manifestations as in tuberculosis. Melioidosis of the spine manifests as spondylodiscitis with paravertebral and prevertebral abscess and presentation as discitis alone is not reported. We report the first case of melioidosis causing isolated discitis without any obvious bony involvement. It also highlights the need for preoperative suspicion of these rare manifestations even in seemingly innocuous disc disease presenting as back pain and radiculopathy.

Tumefactive demyelination-an unusual neurological presentation of HIV.

We describe 3 individuals infected with human immunodeficiency virus with unusual focal brain syndromes; magnetic resonance imaging revealed "open-ring" pattern space occupying lesions. After deterioration while the patients were receiving anti-Toxoplasma therapy, brain biopsy was performed, which revealed aggressive demyelination consistent with tumefactive demyelination. Treatment with high-dose steroids resulted in complete recovery in all cases.

Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations.

Two hundred and twenty-three consecutive patients fulfilling clinical diagnostic criteria for frontotemporal lobar degeneration (FTLD), and 259 patients with motor neuron disease (MND), for whom genomic DNA was available, were investigated for the presence of mutations in tau (MAPT) and progranulin (PGRN) genes. All FTLD patients had undergone longitudinal neuropsychological and clinical assessment, and in 44 cases, the diagnosis had been pathologically confirmed at post-mortem. Six different PGRN mutations were found in 13 (6%) patients with FTLD. Four apparently unrelated patients shared exon Q415X 10 stop codon mutation. However, genotyping data revealed all four patients shared common alleles of 15 SNPs from rs708386 to rs5848, defining a 45.8-kb haplotype containing the whole PGRN gene, suggesting they are related. Three patients shared exon 11 R493X stop codon mutation. Four patients shared exon 10 V452WfsX38 frameshift mutation. Two of these patients were siblings, though not apparently related to the other patients who in turn appeared unrelated. One patient had exon 1 C31LfsX34 frameshift mutation, one had exon 4 Q130SfsX130 frameshift mutation and one had exon 10 Q468X stop codon mutation. In addition, two non-synonymous changes were detected: G168S change in exon 5 was found in a single patient, with no family history, who showed a mixed FTLD/MND picture and A324T change in exon 9 was found in two cases; one case of frontotemporal dementia (FTD) with a sister with FTD+MND and the other in a case of progressive non-fluent aphasia (PNFA) without any apparent family history. MAPT mutations were found in 17 (8%) patients. One patient bore exon 10 + 13 splice mutation, and 16 patients bore exon 10 + 16 splice mutation. When PGRN and MAPT mutation carriers were excluded, there were no significant differences in either the allele or genotype frequencies, or haplotype frequencies, between the FTLD cohort as a whole, or for any clinical diagnostic FTLD subgroup, and 286 controls or between MND cases and controls. However, possession of the A allele of SNP rs9897526, in intron 4 of PGRN, delayed mean age at onset by approximately 4 years. Patients with PGRN and MAPT mutations did not differ significantly from other FTLD cases in terms of gender distribution or total duration of illness. However, a family history of dementia in a first-degree relative was invariably present in MAPT cases, but not always so in PGRN cases. Onset of illness was earlier in MAPT cases compared to PGRN and other FTLD cases. PNFA, combined with limb apraxia was significantly more common in PGRN mutation cases than other FTLD cases. By contrast, the behavioural disorder of FTD combined with semantic impairment was a strong predictor of MAPT mutations. These findings complement recent clinico-pathological findings in suggesting identifiable associations between clinical phenotype and genotype in FTLD.

Pneumococcal meningitis secondary to intra-sphenoidal encephalocoele.

Basal encephalocoeles are rare congenital abnormalities of the skull base. The authors describe a rare case of spontaneous CSF leak and meningitis secondary to an intra-sphenoidal encephalocoele. Initial endoscopic transsphenoidal repair was unsuccessful, necessitating a combined subtemporal and transsphenoidal approach to close the defect.

Dry beriberi mimicking the Guillain-Barre syndrome.

A 44-year-old man is described with severe flaccid quadriparesis that evolved over 3 weeks. He had regularly binged on alcohol-up to 20 cans of beer per day with occasional consumption of spirits-for more than 15 years but had balanced this with regular food intake. However, for a week prior to the current episode he had not eaten anything of significance. Nerve conduction studies revealed a background peripheral, mainly sensory, neuropathy with a superimposed acute motor axonopathy. CSF was normal. He improved with high dose vitamin replacement and physiotherapy but remains dependent on a Zimmer frame for mobility and a splint for wrist drop.

Immune reconstitution associated with progressive multifocal leukoencephalopathy in human immunodeficiency virus: a case discussion and review of the literature.

OBJECTIVES: To report the neuropathological findings of a patient with immune reconstitution syndrome associated with progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV) and to review the literature. METHODS: A 38-year-old man was presented with a rapidly evolving brainstem syndrome. Serology for HIV was positive with an initial CD4 count of 130 cells/mL3. Magnetic resonance imaging showed widespread high signal changes within the brainstem bilaterally, the cerebellum, inferior cerebellar peduncle, and the frontal lobe on the right. Opportunistic infections were excluded from blood and cerebrospinal fluid samples. Despite treatment with antiretrovirals, he continued to deteriorate neurologically, and a repeat magnetic resonance imaging scan showed progression of his lesions. Cortical wedge frontal lobe brain biopsy showed features characteristic of PML, but was associated with an exaggerated inflammatory response. Polymerase chain reaction analysis of the specimen demonstrated the presence of JC virus (JCV) DNA, confirming the pathologic impression of PML. RESULTS: The patient made a rapid (within 24 hours) improvement with pulsed methylprednisolone and has maintained a clinical response 7 months later. These features clinically, radiologically, and histopathologically suggest an added component in the form of immune reconstitution syndrome to PML. CONCLUSION: This report highlights the need to carefully evaluate the clinical syndrome in patients with HIV-associated leukoencephalopathy. It also substantiates the role of corticosteroids in carefully considered cases of HIV with leukoencephalopathy secondary to immune reconstitution.

Cognitive phenotypes in Alzheimer's disease and genetic risk.

Variation in the clinical characteristics of patients with Alzheimer's disease (AD) is increasingly recognised, although the factors underlying variation are not fully understood. The study examined the cognitive characteristics of 523 AD patients at the time of their presentation to a neurological dementia clinic and explored the relationship to family history and apolipoprotein E (APOE) genotype. Distinct profiles were identified, which were mirrored by topographical differences on neuroimaging. Clinical distinctions were maintained over time. Two-thirds of patients showed a constellation of deficits at presentation which included memory, language, visuospatial and constructional difficulties. However, a quarter had circumscribed presentations of amnesia, aphasia, perceptuospatial disorder or apraxia. The rare presence of frontal lobe characteristics was associated with a younger age of onset, an increased incidence of myoclonus at presentation, a positive family history but not with possession of APOE epsilon4 allele. An amnestic presentation (severe, yet circumscribed amnesia) was strongly associated with an older age of onset, a positive family history and the presence of APOE epsilon4 allele. Posterior cortical presentations showed a female bias, were typically sporadic, and showed no association with APOE epsilon4. The findings support the notion of phenotypic variation in AD, and show that genetic risk factors can influence clinical presentation. The findings draw attention to the specific association between APOE epsilon4 allele and memory but challenge the commonly held notion that the presence of the epsilon4 allele inevitably reduces onset age. The findings indicate that risk factors other than APOE epsilon4 allele underlie the non-familial, early onset posterior hemisphere presentations of AD.

Progressive anomia revisited: focal degeneration associated with progranulin gene mutation.

In 2003 we reported a case study of a patient, Newton who presented with a progressive circumscribed anomia in association with focal left hemisphere atrophy. Remarkably, he could spell aloud the names of objects that he could not name, indicating dissociated access to phonology and orthography. We now present follow-up clinical data, post-mortem histopathological findings, and results of molecular genetic analysis. Newton showed tau-negative ubiquitin-positive histology consistent with frontotemporal lobar degeneration (FTLD) and a mutation in the progranulin (PGRN) gene. The case exemplifies the heterogeneity of clinical expression of FTLD and contributes to understanding of primary progressive aphasia.

Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia.

BACKGROUND AND PURPOSE: Virchow-Robin spaces (VRSs) are CSF spaces that accompany blood vessels as they perforate the brain substance. Dilatation of VRS is associated with microangiopathy. Microvascular disease has a major etiologic and pathogenetic role in dementias. To our knowledge, no investigators have looked at the relationship between dilated VRS on MR imaging and cerebral microvascular disease. The aim of our study was to test the hypothesis that dilatation of VRS is associated with subcortical vascular dementia. METHODS: We recruited 75 patients with Alzheimer's disease (n = 35), ischemic vascular dementia (n = 24), or frontotemporal dementia (n = 16) and 35 healthy volunteers. We assessed deep white matter and periventricular hyperintensities and the severity of VRS dilatation, as scored on MR images. Statistical group comparisons and multiple regression analyses were performed to quantify the relationship between imaging features and diagnoses. RESULTS: White matter lesions were more common in patients with ischemic vascular dementia than in those with Alzheimer's disease or healthy volunteers (P < .01). VRS scores were significantly higher in patients with vascular dementia than in patients with AD (P < .001), patients with FTD (P < .01), or healthy volunteers (P < .001). VRS scores accounted for 29% of the variance in the regression model, and scores for periventricular hyperintensity accounted for 2%. CONCLUSION: VRS dilatation is common in diseases associated with microvascular abnormality and can be used as a diagnostic tool to differentiate vascular dementias from degenerative dementias.

Persistent Cryptococcal Brain Infection despite Prolonged Immunorecovery in an HIV-Positive Patient.

Background. HIV-positive people starting combined antiretroviral therapy may develop immune reconstitution to latent or treated opportunistic infections. Immune reconstitution to cerebral Cryptococcus is poorly understood and can be fatal. Case Presentation. A 33-year-old Zimbabwean female presented with cryptococcal meningitis and newly diagnosed HIV with a CD4 count of 51 cells/ µ L (4%). She was treated with amphotericin and flucytosine. Combined antiretroviral therapy was started four weeks later and she showed early improvement. However, over the ensuing 18 months, her clinical course was marked by periodic worsening with symptoms resembling cryptococcal meningitis despite having achieved CD4 counts ≥400 cells/ µ L. Although initially treated for relapsing cryptococcal immune reconstitution syndrome, a brain biopsy taken 17 months after initial presentation showed budding Cryptococci. Conclusion. This unusually protracted case highlights the difficulties in differentiating relapsing cryptococcal meningitis from immune reconstitution and raises questions concerning the optimum timing of initiation of combined antiretroviral therapy in such patients.