Publications by authors named "Andrew F Dean"

14 Publications

  • Page 1 of 1

Periocular Amyloidosis Manifesting as Pseudopemphigoid Treated With Mitomycin C.

Cornea 2017 Apr;36(4):518-520

*Oculoplastics Department, Royal Eye Infirmary, Derriford Hospital, Plymouth, United Kingdom; and †Histopathology Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.

Purpose: To describe an unusual cicatrizing manifestation of periocular amyloid and the utility of adjuvant antimetabolite therapy.

Methods: This is a case report of a 49-year old woman with progressive bilateral upper lid ptosis, who was found to have bilateral inferior forniceal masses with thickening of the conjunctiva. Conjunctival and eyelid biopsies showed evidence of amyloid deposition. Systemic evaluation did not reveal any evidence of systemic amyloidosis. Her blepharoptosis continued to deteriorate, and she underwent bilateral sequential upper lid ptosis correction surgery and debulking procedures. Subsequently, she developed severe and progressive cicatricial conjunctivitis with extensive symblepharon formation in all 4 fornices and restriction of ocular motility, simulating a clinical picture of ocular mucous membrane pemphigoid.

Results: She was treated surgically by division of symblepharon augmented with application of topical mitomycin C intraoperatively. This has been partially successful in freeing up differential movement between her lid and her eye and consequently improving eye protection and lubrication.

Conclusions: Pseudopemphigoid represents a rare manifestation of periocular amyloid. Risks and benefits of surgical procedures in this context need to be carefully weighed to minimize the risk of secondary complications. Topical mitomycin C may be considered as a relatively safe adjunct in managing the cicatricial component of the disease.
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http://dx.doi.org/10.1097/ICO.0000000000001138DOI Listing
April 2017

Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations.

J Neuropathol Exp Neurol 2015 Jul;74(7):688-703

From the Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, UK (NZL, CLA, LH, GF, RM, RWT); East Anglian Medical Genetics Service, Cambridge University Hospital NHS foundations Trust, Cambridge Biomedical Campus, Cambridge, UK (KS, SP); Department of Paediatric Neurology, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge UK (DK); Neonatal Unit, The Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (AO); The Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Du Cane Road, London, UK (CL); Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK (RHK); Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK (IPH); Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Trust, Oxford, UK (GKB); and Department of Histopathology, Cambridge University Hospital NHS foundations Trust, Cambridge, UK (AFD).

Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Enzyme histochemistry of postmortem tissues revealed a near-global cytochrome c oxidase-deficiency; assessment of respiratory chain enzyme activities confirmed severe deficiencies involving complexes I, III, and IV. Molecular genetic studies revealed 2 RARS2 gene mutations: a c.1A>G, p.? variant predicted to abolish the initiator methionine, and a deep intronic c.613-3927C>T variant causing skipping of exons 6-8 in the mature RARS2 transcript. Neuropathologic investigation included low brain weights, small brainstem and cerebellum, deep cerebral white matter pathology, pontine nucleus neuron loss (in 1 sibling), and peripheral nerve pathology. Mitochondrial respiratory chain immunohistochemistry in brain tissues confirmed an absence of complexes I and IV immunoreactivity with sparing of mitochondrial numbers. These cases expand the clinical spectrum of RARS2 mutations, including antenatal features and widespread mitochondrial respiratory chain deficiencies in postmortem brain tissues.
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http://dx.doi.org/10.1097/NEN.0000000000000209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470523PMC
July 2015

The genome of the sparganosis tapeworm Spirometra erinaceieuropaei isolated from the biopsy of a migrating brain lesion.

Genome Biol 2014 ;15(11):510

Background: Sparganosis is an infection with a larval Diphyllobothriidea tapeworm. From a rare cerebral case presented at a clinic in the UK, DNA was recovered from a biopsy sample and used to determine the causative species as Spirometra erinaceieuropaei through sequencing of the cox1 gene. From the same DNA, we have produced a draft genome, the first of its kind for this species, and used it to perform a comparative genomics analysis and to investigate known and potential tapeworm drug targets in this tapeworm.

Results: The 1.26 Gb draft genome of S. erinaceieuropaei is currently the largest reported for any flatworm. Through investigation of β-tubulin genes, we predict that S. erinaceieuropaei larvae are insensitive to the tapeworm drug albendazole. We find that many putative tapeworm drug targets are also present in S. erinaceieuropaei, allowing possible cross application of new drugs. In comparison to other sequenced tapeworm species we observe expansion of protease classes, and of Kuntiz-type protease inhibitors. Expanded gene families in this tapeworm also include those that are involved in processes that add post-translational diversity to the protein landscape, intracellular transport, transcriptional regulation and detoxification.

Conclusions: The S. erinaceieuropaei genome begins to give us insight into an order of tapeworms previously uncharacterized at the genome-wide level. From a single clinical case we have begun to sketch a picture of the characteristics of these organisms. Finally, our work represents a significant technological achievement as we present a draft genome sequence of a rare tapeworm, and from a small amount of starting material.
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http://dx.doi.org/10.1186/PREACCEPT-2413673241432389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265353PMC
July 2015

Atypical Presentation of Low-Grade Small Lymphocytic Lymphoma of the Lacrimal Sac.

Ophthalmic Plast Reconstr Surg 2015 Nov-Dec;31(6):e163-5

*Adnexal Service, and †Department of Histopathology, Addenbrooke's Hospital, Cambridge, United Kingdom.

Lymphoma of the lacrimal sac is uncommon and usually presents as a lacrimal sac mass, against a background of known systemic lymphoma. This study presents the case of a 70-year-old man with small lymphocytic lymphoma of the lacrimal sac and widespread systemic involvement presenting as common canalicular obstruction without a palpable mass or systemic symptoms.
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http://dx.doi.org/10.1097/IOP.0000000000000188DOI Listing
June 2016

Giant intracranial hemangioma in a neonate.

Acta Neurochir (Wien) 2014 Jun 5;156(6):1151-4. Epub 2014 Feb 5.

Department of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK,

In this report we detail the case of an infant presenting with a giant intracranial congenital hemangioma and describe the clinical features and surgical management. Congenital hemangiomas are benign vascular tumors that typically present as skin lesions in neonates and infants. On rare occasions they present as intracranial tumors. The possibility that these tumors may undergo spontaneous regression poses a treatment dilemma.
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http://dx.doi.org/10.1007/s00701-014-2007-yDOI Listing
June 2014

A 73 year-old man with a mass at the foramen magnum.

Brain Pathol 2013 Nov;23(6):699-702

Department of Neuropathology Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.1111/bpa.12091DOI Listing
November 2013

Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study.

J Neuropathol Exp Neurol 2013 Feb;72(2):164-75

Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, UK.

Mitochondrial respiratory chain disease is associated with a spectrum of clinical presentations and considerable genetic heterogeneity. Here we report molecular genetic and neuropathologic findings from an adult with an unusual manifestation of mitochondrial DNA disease. Clinical features included early-onset cataracts, ataxia, and progressive paraparesis, with sequencing revealing the presence of a novel de novo m.14685G>A mitochondrial tRNA(Glu) (MT-TE) gene mutation. Muscle biopsy showed that 13% and 34% of muscle fibers lacked cytochrome c oxidase activity and complex I subunit expression, respectively. Biochemical studies confirmed a marked decrease in complex I activity. Neuropathologic investigation revealed a large cystic lesion affecting the left putamen, caudate nucleus, and internal capsule, with evidence of marked microvacuolation, neuron loss, perivascular lacunae, and blood vessel mineralization. The internal capsule showed focal axonal loss, whereas brainstem and spinal cord showed descending anterograde degeneration in medullary pyramids and corticospinal tracts. In agreement with muscle biopsy findings, reduced complex I immunoreactivity was detected in the remaining neuronal populations, particularly in the basal ganglia and cerebellum, correlating with the neurologic dysfunction exhibited by the patient. This study emphasizes the importance of molecular genetic and postmortem neuropathologic analyses for furthering our understanding of underlying mechanisms of mitochondrial disorders.
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http://dx.doi.org/10.1097/NEN.0b013e31828129c5DOI Listing
February 2013

Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk.

J Lipid Res 2011 Nov 23;52(11):1885-926. Epub 2011 Aug 23.

Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle- and old-age. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specific membrane transporter systems (NPC1L1, ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classification of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means.
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http://dx.doi.org/10.1194/jlr.R017855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284125PMC
November 2011

'Radiologically compatible CLIPPERS' may conceal a number of pathologies.

Brain 2011 Aug 7;134(Pt 8):e187. Epub 2011 Jun 7.

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http://dx.doi.org/10.1093/brain/awr134DOI Listing
August 2011

Internal auditory canal metastasis mimicking a vestibular schwannoma at presentation - a case report and review of the literature.

Int Semin Surg Oncol 2009 Mar 31;6. Epub 2009 Mar 31.

Department of Oncology, Essex County Hospital, Lexden Road, Colchester, Essex CO3 3NB, UK.

Metastasis to the internal auditory canal from breast carcinoma is extremely rare and difficult to diagnose. It radiologically mimics vestibular schwannoma and can occur as a first manifestation of systemic relapse after a long disease-free interval in patients previously treated for early breast cancer. The diagnosis is usually made retrospectively and the optimal management of such metastasis following complete resection remains undefined.
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http://dx.doi.org/10.1186/1477-7800-6-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670313PMC
March 2009

Amyotrophic lateral sclerosis with sensory neuropathy: part of a multisystem disorder?

J Neurol Neurosurg Psychiatry 2007 Jul;78(7):750-3

King's College London MRC Centre for Neurodegeneration Research, Department of Neurology, Institute of Psychiatry, London, UK.

Sensory involvement is thought not to be a feature of amyotrophic lateral sclerosis (ALS). However, in the setting of a specialist motor neuron disease clinic, we have identified five patients with sporadic ALS and a sensory neuropathy for which an alternative cause could not be identified. In three individuals, sensory nerve biopsy was performed, demonstrating axonal loss without features of an alternative aetiology. These findings support the hypothesis that ALS is a multisystem neurodegenerative disorder that may occasionally include sensory neuropathy among its non-motor features.
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http://dx.doi.org/10.1136/jnnp.2006.098798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117693PMC
July 2007

Reversible parkinsonism in a patient with progressive multifocal leucoencephalopathy.

J Neurol Neurosurg Psychiatry 2007 Apr;78(4):408-10

Department of Clinical Neurosciences, University of Cambridge and Addenbrooke's Hospital, Cambridge, UK.

A case of pathologically confirmed progressive multifocal leucoencephalopathy presenting with unilateral parkinsonism and cognitive decline that significantly improved over a 12-month period without any treatment is described. The patient had a background of chronic lymphocytic leukaemia, but had been in complete remission for 4 years at the time of diagnosis. This case is highly unusual not only in terms of the mode of clinical presentation in an apparently immunocompetent patient but also in that the patient spontaneously improved without any intervention. Progressive multifocal leucoencephalopathy should therefore be considered in the differential diagnosis of movement disorders developing in patients with a history of lymphoproliferative disease, even if they are in remission. Furthermore, such cases may not always require treatment, as the patient's immune system may overcome the viral disease process with spontaneous resolution of their neurological disorder.
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http://dx.doi.org/10.1136/jnnp.2006.103259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077773PMC
April 2007

Abnormal prion protein in the pituitary in sporadic and variant Creutzfeldt-Jakob disease.

J Gen Virol 2007 Mar;88(Pt 3):1068-1072

National Creutzfeldt-Jakob Disease Surveillance Unit (NCJDSU) and Division of Pathology, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.

By using high-sensitivity Western blotting and immunohistochemistry, pituitary glands from patients with sporadic and variant Creutzfeldt-Jakob disease (sCJD and vCJD, respectively) were analysed for the presence of the protease-resistant form of the prion protein (PrPres). PrPres was detected in a greater proportion of vCJD pituitaries than sCJD pituitaries and was localized predominantly in the neurohypophysis. PrPres was also detected in a recurrent pituitary adenoma from an sCJD patient. Immunohistochemical analysis showed sparse positive labelling, predominantly in folliculostellate cells, in vCJD and sCJD adenohypophyses. The PrPres glycosylation pattern in the vCJD neurohypophyses showed a predominance of the unglycosylated band, which differed markedly from patterns found in all other vCJD tissues. The presence of PrPres in the pituitary of CJD patients at autopsy suggests that human growth hormone-related iatrogenic CJD may have indeed resulted from infectivity in collected pituitaries rather than necessarily from contamination of pituitary pools by adjacent brain tissue.
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http://dx.doi.org/10.1099/vir.0.81913-0DOI Listing
March 2007

Chromosomal imbalances in meningeal solitary fibrous tumors.

Cancer Genet Cytogenet 2002 Jun;135(2):160-4

Department of Neurosurgery, King's College Hospital, Denmark Hill, London, UK.

We present the results of a comparative genomic hybridization (CGH) analysis of three meningeal solitary fibrous tumors (SFT). One case showed loss of chromosome 3 and two tumors had deletions of the region 3p21-p26. Other chromosomal losses included 4p15, 8q22-q24, 10, 11q14-q25, 17q11- q23, 20, and 21 in one case each. In addition, there were gains of 18p11-p13 in one case, and 1p11-p36 and 20q11-q13 in another. To our knowledge, there are no previous CGH or cytogenetic data on meningeal SFT, and loss of material on chromosome 3 has not been described in SFT at other sites. Our findings are discussed in relation to published molecular genetic and cytogenetic data on meningioma and hemangiopericytoma, the two lesions with which meningeal SFT are most likely to be confused.
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http://dx.doi.org/10.1016/s0165-4608(01)00646-xDOI Listing
June 2002