Aruna Chakrabarty

[18F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease: Specific detection of advanced phases of amyloid-β pathology

Amyloid positron emission tomography (PET) has become an important tool to identify amyloid‐β (Aβ) pathology in Alzheimers disease (AD) patients. Here, we determined the diagnostic value of the amyloid PET tracer [18F]flutemetamol in relation to Aβ pathology at autopsy.

Early-onset Lafora body disease

The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht-Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and causes translocation of the two proteins to the nucleus. We find that Phe261Leu-PRDM8 results in excessive sequestration of laforin and malin in the nucleus and that it therefore likely represents a gain-of-function mutation that leads to an effective deficiency of cytoplasmic laforin and malin. We have identified a new progressive myoclonus epilepsy with Lafora bodies, early-onset Lafora body disease, 101 years after Lafora disease was first described. The results to date suggest that PRDM8, the early-onset Lafora body disease protein, regulates the cytoplasmic quantities of the Lafora disease enzymes.

Malignant transformation in pleomorphic xanthoastrocytoma--a report of two cases.

Pleomorphic xanthoastrocytomas (PXA) with malignant transformation are reported in two adult men with a long history of seizures, recent onset of neurological symptoms and superficially located, temporal lobe lesions. Although PXA is generally described as having relatively benign behaviour, this report adds two further cases of malignant transformation to the literature.

Meningioangiomatosis: a case report and review of the literature.

A case of cerebral meningioangiomatosis in an adult man without any stigmata of neurofibromatosis is reported. A 22 year-old man with no previous neurological history, presented with adversive seizures; clinical examination and electro-encephalogram were normal. CT showed nodular calcified masses in the left frontal lobe and in the left posterior parietal area. A craniotomy was performed and the frontal lesion was excised. Histological examination showed a predominantly intracerebral tumour involving both grey and white matter, with a complex picture of variable cellularity, dense calcification and prominent perivascular arrangements of reticulin-rich spindle cell fascicles with palisade formation widely involving the brain tissue. Immunohistochemistry for S100 protein varied between different parts of the tumour; there was focal positivity for S100 protein and smooth muscle actin in the lesion with no reaction for GFAP or EMA. Immunostaining for Factor 8-related antigen highlighted the perivascular arrangement of lesional cells and demonstrated an increase in the number of small vessels in other areas. Electron microscopy of the main mass showed elongated spindle cells with formation of pericellular basal lamina. The literature on meningioangiomatosis was reviewed. The evidence for meningeal, perivascular neural plexus or pericyte origin does not appear to be well founded. The present case further illustrates the difficulty in identifying an exact histogenetic cell and probably reflects an origin from a primitive perivascular mesenchymal cell.

MIB1 proliferation index in meningiomas: does it predict recurrence? A clinicopathological study.

The usefulness of proliferation marker MIB1 in predicting recurrences in cranial meningiomas when other clinical and pathological factors are considered was assessed. Data from 65 patients with meningiomas were analysed and their clinical notes reviewed to define the Simpson grade of surgical excision, the location of tumour, amongst other clinical factors. The diagnosis was reviewed; immunohistochemical staining for a proliferation marker MIB1 was carried out on archival formalin-fixed, paraffin-embedded tumour and a labelling index for MIB1 (MIB1 L1) calculated. Analysis was undertaken of the impact of histology, grade of excision, tumour location and proliferation index on the risk of recurrence. The grade of surgical resection and histology type were the most important factors likely to predict recurrence. MIB1 LI was not considered useful in predicting tumour recurrence.

Olfactory groove schwannoma revisited.

Schwannomas are benign, slowly growing nerve sheath tumours. They can arise from any peripheral nerve containing Schwann cells including distal portions of cranial nerves. The optic and olfactory nerves do not have a Schwann cell layer and therefore do not develop schwannomas. We report a very unusual case of a young woman who presented with partial seizures and had radiological and operative features of an olfactory groove meningioma. However, subsequent histological analysis revealed the tumour was in fact a schwannoma.

Ependymoma of the neurohypophysis

There are two reported cases of ependymomas arising in the pituitary fossa; one in a human, the other in a horse. Both died during their stay in hospital. The case presented here is the first published case of a patient who is well 3 months after surgery.

Occurrence and distribution of pilomyxoid astrocytoma

Abstract Purpose. To know the occurrence and distribution of Pilomyxoid Astrocytomas amongst tumours previously diagnosed histologically as Pilocytic Astrocytoma and to assess the clinical impact of this new entity. Methods. Retrospective Diagnostic review of all cases histologically diagnosed as WHO Grade I Astrocytoma at a single Neurosurgical unit between 1990 and 2003. Results. Of a total of 91 cases identified, 9 were found to have Pilomyxoid histology. Of these, 8 were children (mean age 3.33 years) and 1 adult. 6 tumours were hypothalamochiasmatic in location. The clinical course of Pilomyxoid tumours was aggressive marked by maturation, multiple recurrences and disease control was rarely achieved with single treatment modality as opposed to typical pilocytics. The overall survival of the pilomyxoid group was not statistically different from the pilocytic tumours. Conclusions. Encompassing all age-groups and locations, Pilomyxoid Astrocytomas constitute about 10% of all tumours previously diagnosed as Pilocytic Astrocytoma. Nearly two-thirds are hypothalamo-chiasmatic in location. Knowledge of this entity is essential for appropriate aggressive treatment and follow-up.

Craniopharyngioma invading the nasal and paranasal spaces, and presenting as nasal obstruction

A case of craniopharyngioma invading the nasal and paranasal sinuses and presenting as nasal obstruction is reported. Imaging showed a destructive mass of the skull base with involvement of the nose and paranasal sinuses. In the excised mass mitoses were frequent and the proliferation index was high. Invasion of the nasopharynx and presentation as a nasopharyngeal mass is uncommon for a craniopharyngioma.

Malignant transformation in pleomorphic xanthoastrocytomaa - report of two cases

Pleomorphic xanthoastrocytomas (PXA) with malignant transformation are reported in two adult men with a long history of seizures, recent onset of neurological symptoms and superficially located, temporal lobe lesions. Although PXA is generally described as having relatively benign behaviour, this report adds two further cases of malignant transformation to the literature.