Relapsing cerebral amyloid angiopathy-related inflammation: the wax and the wane.

Cerebral amyloid angiopathy-related inflammation (CAA-I) is a rare variant of cerebral amyloid angiopathy (CAA). Its precise pathophysiology remains uncertain and we currently have limited evidence on which immunosuppressive agents are the most effective in its treatment. The disease course of CAA-I disorders can vary from an isolated clinical event to recurrent episodes. We present a case of biopsy-confirmed CAA-I that gives insight into its potential relapsing nature and the challenges of its long-term management.

Cervical epidural extra-osseous Ewing sarcoma mimicking an epidural abscess.

We report a case of a 21-year-old woman presenting with quadriplegia which was initially diagnosed with an epidural abscess in view of her MR scan and raised inflammatory marker levels. Histology revealed an epidural extra-osseous Ewing's sarcoma (EES). Epidural location of EES is a very rare condition which can be very challenging to diagnose. Early diagnosis and surgical excision followed by chemotherapy represent the main stem of management.

Do NIA-AA criteria distinguish Alzheimer's disease from frontotemporal dementia?

BACKGROUND: Clinical criteria are important for improving diagnostic accuracy and ensuring comparability of patient cohorts in research studies. OBJECTIVE: The aim was to assess the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer's disease (AD) dementia in AD and frontotemporal lobar degeneration (FTLD). METHODS: Two hundred twelve consecutive patients with pathologically confirmed AD or FTLD who were clinically assessed in a specialist cognitive unit were identified. Fifty-five patients were excluded predominantly because of insufficient clinical information. Anonymized clinical data were rated against the NIA-AA criteria by raters who were blinded to clinical and pathologic diagnosis. RESULTS: The NIA-AA AD dementia criteria had a sensitivity of 65.6% for probable and 79.5% for possible AD and a specificity of 95.2% and 94.0% for probable and possible, respectively. CONCLUSION: In patients with FTLD and predominantly early-onset AD, the NIA-AA AD dementia criteria have high specificity but lower sensitivity. The high specificity is due to the broad exclusion criteria.

Pathological correlates of frontotemporal lobar degeneration in the elderly.

Frontotemporal lobar degeneration (FTLD) is generally recognised as a disorder with presenile onset (that is before 65 years of age) with only occasional cases presenting later than this. We set out to determine what proportion of cases of FTLD had late onset of disease and whether such cases of FTLD had distinctive clinical and neuropathological features as compared to cases with presenile onset. Within a combined Manchester and Newcastle autopsy series of 117 cases with pathologically confirmed FTLD (109/117 cases also met Lund Manchester clinical criteria for FTLD), we identified 30 cases (onset age range 65-86 years), comprising 25% of all FTLD cases ascertained in these two centres over a 25-year period. Neuropathologically, the 30 elderly cases presented features of several FTLD histological subgroups [FTLD-TDP (types 1, 2 and 3, 19 cases (63%)], FLTD-tau [MAPT, PiD and CBD, 10 cases (33%)] and FTLD-UPS (1 case), similar in range of phenotypes to that seen in the presenile group, though patients with MAPT, but not PGRN, mutation, or FUS pathology, were notably absent or fewer in the elderly group. Hippocampal sclerosis (HS) was present in 13/30 of the elderly FTLD cases (43%) compared with 14/79 (18%) (P = 0.012) in the presenile FTLD patients. Lobar atrophy present in most of the younger patients was prominent in only 25% of the elderly subjects. Prospective and retrospective psychiatric and medical case note analysis showed that the majority of the elderly FTLD patients, like their younger counterparts, had behavioural features consistent with frontotemporal dementia. FTLD is common amongst elderly persons and all or most of the major clinical and histological subtypes present in younger individuals can be seen in the older group.

Radiotherapy-induced supratentorial primitive neuroectodermal tumour in a 17-year-old female: a case report and review of the literature.

We report a case of a 17-year-old female who presented with a CNS primitive neuroectodermal tumour 12 years after cranial radiotherapy for relapsed childhood acute lymphoblastic leukaemia. In this article, we discuss the association of these rare tumours with previous craniospinal irradiation and review the pertinent literature.

A Comparative Study of Pathological Outcomes in The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age and Brains for Dementia Research Cohorts.

In the present study, we have characterized and compared individuals whose brains were donated as part of The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (UoM) with those donated through the Manchester arm of the UK Brains for Dementia Research (BDR) program. The aim of this study was to investigate how differences in study recruitment may affect final pathological composition of cohort studies. The UoM cohort was established as a longitudinal study of aging and cognition whereas the BDR program was established, prima facie, to collect brains from both demented and non-demented individuals for the purpose of building a tissue research resource. Consequently, the differences in recruitment patterns generated differences in demographic, clinical, and neuropathological characteristics. There was a higher proportion of recruits with dementia [mostly Alzheimer's disease (AD)] within the BDR cohort than in the UoM cohort. In pathological terms, the BDR cohort was more 'polarized', being more composed of demented cases with high Braak pathology scores and non-demented cases with low Braak scores, and fewer non-AD pathology cases, than the UoM cohort. In both cohorts, cerebral amyloid angiopathy tended to be greater in demented than non-demented individuals. Such observations partly reflect the recruitment of demented and non-demented individuals into the BDR cohort, and also that insufficient study time may have elapsed for disease onset and development in non-demented individuals to take place. Conversely, in the UoM cohort, where there had been nearly 30 years of study time, a broader spread of AD-type pathological changes had 'naturally' evolved in the brains of both demented and non-demented participants.

Small vessel multi-organ vasculitis and marantic endocarditis complicating rheumatoid arthritis.

Marantic endocarditis is an extremely rare extra-articular complication of rheumatoid arthritis. To date, documented cases typically occurred in the absence of other systemic features of disease activity. We report a rare and exceptional example of marantic endocarditis secondary to fulminant systemic rheumatoid vasculitis with multi-organ disease. Findings from this case and literature review suggest that marantic endocarditis associated with rheumatoid vasculitis displays a tendency to affect the mitral valve with high risk of embolization.

Calcifying pseudoneoplasm of the neuraxis (CaPNoN): an unusual cause of third nerve palsy in a teenager.

An 18-year-old part-time teacher presented with headache and diplopia. Physical examination showed partial left oculomotor palsy. Neurology examination was otherwise unremarkable. Cross-sectional imaging was arranged for investigation of third nerve palsy. On CT scan, the lesion was calcified, and on MRI, hypointense on T 1 and T 2 weightedimages with thin rim enhancement, resembling an atypical meningioma. CT angiogram showed no vascular connection. Following worsening diplopia and a slight increase in lesion size on follow-up MRI, the patient was re-reviewed in our regional skull base multidisciplinary team meeting, where a decision for excision was made. Pre-operatively, the absence of a vascular connection was confirmed on catheter angiogram. Histopathological examination demonstrated features typical of calcified pseudoneoplasm of the neuraxis, with extensive metaplastic calcification with stroma containing variable fibrovascular tissue and focal inflammatory cell infiltrates, spindle and epithelioid cells, and psammoma bodies at the rim of the lesion. Following surgery, the patient had persisting diplopia. He remains under clinical review. As surgical resection is considered curative, no further imaging follow-up is planned.

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration.

BACKGROUND/OBJECTIVES: We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. METHODS: Eighty-one dementia patients with pathological confirmation of FTLD were identified. Anonymized clinical records from patients' first assessment were rated for language and behavioural features from frontotemporal dementia consensus criteria, primary progressive aphasia (PPA) criteria and 1998 FTLD criteria. RESULTS: Over 90% of patients with FTLD pathology exhibited a combination of at least one behavioural and one language feature. Changes in language, in particular, were commonly accompanied by behavioural change. Notably, the majority of patients who displayed language features characteristic of semantic variant PPA exhibited 'early perseverative, stereotyped or compulsive/ritualistic behaviour'. Moreover, 'executive/generation deficits with relative sparing of memory and visuospatial functions' occurred in most patients with core features of non-fluent variant PPA. CONCLUSION: Behavioural and language symptoms frequently co-occur in patients with FTLD pathology. Current classifications, which separate behavioural and language syndromes, do not reflect this co-occurrence.

Woman aged 24 years with fourth ventricular mass.

April 2005. A woman aged 24 years presented with symptoms related to a tumor in the fourth ventricle. Cytologically, the tumor was biphasic with areas typical of a classic ependymoma, including rosettes, and other areas containing grossly atypical giant cells. Many tumor cells were GFAP-positive and ultrastructural examination revealed microvilli and cilia. The histopathologic abnormalities place this tumor among the ependymomas. Its focal giant cell phenotype is very rare, but has been reported in 4 intracranial or filum ependymomas.

Lymphocytic hypophysitis in males.

Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary gland that typically affects women in the peripartum period. We describe two male patients (ages 43 years and 36 years), who presented with headaches, visual disturbance and hypopituitarism. MRI revealed a heterogeneous pituitary lesion that extended into the suprasellar region and with a thickened pituitary stalk. In both patients a histopathological diagnosis of LH was made after endoscopic transsphenoidal surgery. LH in males, although rare, should be considered as a differential diagnosis in those with hypopituitarism and a heterogeneous pituitary fossa mass, extending into pituitary stalk.

Visual loss from a pituitary mass: collision tumors of prostatic metastasis and suprasellar meningioma.

Central nervous system spread from prostate cancer is typically associated with raised prostate specific antigen (PSA) levels. The authors describe a unique case of a "collision tumor" of a prostatic metastasis to the pituitary, juxtaposed to a suprasellar meningioma, with normal PSA levels. This case also emphasizes the need to consider prostatic metastasis in the differential diagnosis of a pituitary mass in patients with a known prostatic cancer, despite the normal PSA levels.

Aspergillosis sinusitis with cranio-orbital spread in an apparently immunocompetent patient.

Intracranial fungal infections are unusual and typically described in immunocompromised hosts. The authors describe a rare case of an immunocompetent white man presenting with blindness after Aspergillus fumigatus infection of the ethmoidal air sinus with spread to the orbital apex and the frontal lobe. This was successfully treated by surgical drainage via a frontal craniotomy and long-term antifungal therapy with voriconazole.

The m.3291T>C mt-tRNA(Leu(UUR)) mutation is definitely pathogenic and causes multisystem mitochondrial disease.

Mitochondrial tRNA point mutations are important causes of human disease, and have been associated with a diverse range of clinical phenotypes. Definitively proving the pathogenicity of any given mt-tRNA mutation requires combined molecular, genetic and functional studies. Subsequent evaluation of the mutation using a pathogenicity scoring system is often very helpful in concluding whether or not the mutation is causing disease. Despite several independent reports linking the m.3291T>C mutation to disease in humans, albeit in association with several different phenotypes, its pathogenicity remains controversial. A lack of conclusive functional evidence and an over-emphasis on the poor evolutionary conservation of the affected nucleotide have contributed to this controversy. Here we describe an adult patient who presented with deafness and lipomas and evidence of mitochondrial abnormalities in his muscle biopsy, who harbours the m.3291T>C mutation, providing conclusive evidence of pathogenicity through analysis of mutation segregation with cytochrome c oxidase (COX) deficiency in single muscle fibres, underlining the importance of performing functional studies when assessing pathogenicity.

Sensitivity and specificity of FTDC criteria for behavioral variant frontotemporal dementia.

OBJECTIVE: We aimed to assess sensitivity and specificity of the updated criteria for behavioral variant frontotemporal dementia (bvFTD) based on a large autopsy-confirmed cohort of patients with dementia. METHODS: Two hundred thirty-nine consecutive pathologically confirmed dementia patients, clinically assessed in a specialist cognitive unit were identified. Patients with predominant aphasia, motor disorders, or insufficient clinical information were excluded. Frontotemporal Dementia Consensus criteria were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis. RESULTS: The final study cohort comprised 156 patients with predominantly early-onset dementia. The updated criteria for possible bvFTD had a sensitivity of 95% and specificity of 82%. Probable bvFTD criteria had a sensitivity of 85% and specificity of 95%. False positives were predominantly patients with presenile Alzheimer disease. CONCLUSION: Revised diagnostic criteria show encouragingly high sensitivity and specificity when applied to patients with early-onset dementia. They therefore provide a useful tool both for specialist researchers and general clinicians. There is a need for further prospective studies of sensitivity and specificity involving a broader spectrum of patients with dementia.

Classification and pathology of primary progressive aphasia.

OBJECTIVE: We aimed to determine the extent to which patients with progressive language impairment conform to 2011 primary progressive aphasia (PPA) classification and to examine clinicopathologic correlations within PPA variants. METHODS: Sixty-two consecutive patients with pathologically confirmed dementia who presented clinically with aphasia were identified. Patients with insufficient clinical information were excluded. PPA classifications were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis. RESULTS: The final cohort comprised 52 patients, 30 of whom met basic PPA criteria. Twenty-five patients met one of the 3 PPA classifications (13 logopenic, 8 nonfluent/agrammatic, and 4 semantic). Five patients did not meet the criteria for any of the PPA variants. All patients who met semantic variant PPA and 75% of patients who met nonfluent/agrammatic variant PPA classifications had frontotemporal lobar degeneration spectrum pathology. Pathologies were heterogeneous in patients who met logopenic variant PPA criteria (46% Alzheimer disease [AD], 8% AD mixed with dementia with Lewy bodies, 23% frontotemporal lobar degeneration, and 23% other). CONCLUSION: The 2011 PPA recommendations classify a large proportion of patients who meet basic PPA criteria. However, some patients had aphasic syndromes that could not be classified, suggesting that the 2011 recommendations do not cover the full range of PPA variants. Classification of semantic variant PPA provides a good prediction of underlying pathology. Classification of logopenic variant does not successfully differentiate PPA due to AD from PPA due to other pathologies.

Neuroglial cyst of the sacral canal. Case report.

Spinal neuroglial cysts are rare. Although there are a few case reports, none describe such cysts within the sacral canal. The authors describe the case of a 29-year-old man who presented with symptoms of urinary retention over a period of several months. Imaging of his lumbar spine demonstrated the presence of an extradural cystic lesion within the sacral canal. He underwent resection of the cyst, with complete reversal of his bladder impairment. Histopathological studies confirmed the presence of a sacral neuroglial cyst.