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Am J Hum Genet 2019 Apr 21;104(4):731-737. Epub 2019 Mar 21.

Department of Genetics, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh 12371, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia. Electronic address:

Ciliopathies are clinical disorders of the primary cilium with widely recognized phenotypic and genetic heterogeneity. In two Arab consanguineous families, we mapped a ciliopathy phenotype that most closely matches Joubert syndrome (hypotonia, developmental delay, typical facies, oculomotor apraxia, polydactyly, and subtle posterior fossa abnormalities) to a single locus in which a founder homozygous truncating variant in FAM149B1 was identified by exome sequencing. We subsequently identified a third Arab consanguineous multiplex family in which the phenotype of Joubert syndrome/oral-facial-digital syndrome (OFD VI) was found to co-segregate with the same founder variant in FAM149B1. Read More

Neuroimage Clin 2018 5;19:454-465. Epub 2018 Apr 5.

Psychiatric Neuroimaging Program, Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.

The () gene was identified in 2002 as responsible for XLAG syndrome, a lissencephaly characterized by an almost complete absence of cortical GABAergic interneurons, and for milder forms of X-linked Intellectual Disability (ID) without apparent brain abnormalities. The most frequent mutation found in the gene, a duplication of 24 base pairs (c.429_452dup24) in exon 2, results in a recognizable syndrome in which patients present ID without primary motor impairment, but with a very specific upper limb distal motor apraxia associated with a pathognomonic hand-grip, described as developmental Limb Kinetic Apraxia (LKA). Read More

Neurocase 2018 Jun 8;24(3):133-139. Epub 2018 Jun 8.

a Neuropsychology and Language Disorders Unit, Department of Neurology , School of Medicine, National and Kapodistrian University of Athens , Greece.

A 74 year-old woman (MD), free of previous neurological history, presented with difficulty in handling cutlery, clothes, writing with what was initially described as an atypical apraxia in acts related to space. Initial neurological evaluation revealed mixed, asymmetric pyramidal, and extrapyramidal semiology. Νeuropsychological testing revealed dressing and constructional deficits, ideomotor apraxia and signs of executive dysfunction in absence of memory, language, and visual perception pathology. Read More

Eur J Vasc Endovasc Surg 2018 06 22;55(6):861-866. Epub 2018 Apr 22.

European Vascular Centre Aachen-Maastricht, Department of Vascular Surgery, University Hospital RWTH Aachen, Aachen, Germany.

Objective: The safety and feasibility of supra-aortic debranching as part of endovascular aortic surgery or as a treatment option for arterial occlusive disease (AOD) remains controversial. The aim of this study was to assess the clinical outcome of this surgery.

Methods: This single centre, retrospective study included 107 patients (mean age 69. Read More

Clin J Am Soc Nephrol 2017 Dec 16;12(12):1974-1983. Epub 2017 Nov 16.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Genetic heterogeneity and phenotypic variability are major challenges in familial nephronophthisis and related ciliopathies. To date, mutations in 20 different genes ( to ) have been identified causing either isolated kidney disease or complex multiorgan disorders. In this study, we provide a comprehensive and detailed characterization of 152 children with a special focus on extrarenal organ involvement and the long-term development of ESRD. Read More

Prion 2017 11 13;11(6):440-453. Epub 2017 Nov 13.

b Department of Nuclear Medicine , Nîmes University Hospital , Nîmes , France.

Objective: To assess the relationship between clinical pattern and cerebral glucose metabolism on [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in Creutzfeldt-Jakob disease (CJD).

Methods: Predefined clinical signs (ataxia, visual, pyramidal, myoclonus, limb apraxia, limb dystonia, sensory, parkinsonism, and corticobasal syndrome [CBS]) and FDG-PET data were assessed in consecutive CJD patients. Two types of statistical parametric mapping (SPM) analyses, using stringent level of significance p < 0. Read More

Am J Med Genet A 2017 Dec 20;173(12):3231-3237. Epub 2017 Oct 20.

NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.

Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Read More

Epileptic Disord 2017 Sep;19(3):345-350

Laboratoire de Cartographie Fonctionnelle du Cerveau, Hôpital Erasme, Université libre de Bruxelles (ULB), Brussels, Department of Pediatric Neurology, Centre Hospitalier Universitaire d'Angers, Angers, France.

Epileptic encephalopathies with continuous spike-and-waves during sleep (CSWS) are characterized by cognitive or language impairment, and are occasionally associated with pathogenic variants of the GRIN2A gene. In these disorders, speech dysfunction could be either related to cerebral dysfunction caused by the GRIN2A deleterious variant or intense interictal epileptic activity. Here, we present a patient with apraxia of speech, clearly linked to severity of epilepsy, carrying a GRIN2A variant. Read More

Med Sci Monit 2017 Apr 9;23:1719-1724. Epub 2017 Apr 9.

Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).

BACKGROUND The etiology of strabismus has a genetic component. Our study aimed to localize the candidate causative gene mutant in a Chinese family with strabismus and to describe its underlying etiology. MATERIAL AND METHODS Genomic DNA was extracted from the affected individual and his parents in a Chinese pedigree with strabismus. Read More

Am J Med Genet A 2017 May 27;173(5):1358-1363. Epub 2017 Mar 27.

Developmental Neurology Unit, Department of Pediatric Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

ZC4H2 is involved in human brain development, and, if mutated, can be responsible for a rare X-linked disorder, originally presented in literature as Wieacker-Wolff syndrome and Miles-Carpenter syndrome. In males, severe intellectual disability is associated with variable symptoms of central and peripheral nervous system involvement, such as spasticity, hyperreflexia, muscle weakness, and arthrogryposis. Female carriers are usually described as asymptomatic or only mildly affected. Read More

Nature 2017 01 21;541(7635):87-91. Epub 2016 Dec 21.

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RH, UK.

XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair. Here we show that biallelic mutations in the human XRCC1 gene are associated with ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia. Cells from a patient with mutations in XRCC1 exhibited not only reduced rates of single-strand break repair but also elevated levels of protein ADP-ribosylation. Read More

Sudan J Paediatr 2016 ;16(1):53-7

Surgical Department, Radiology Division, Hadhramout University College of Medicine , Hadhramout Governorate , Yemen.

Joubert syndrome is a rare autosomal recessive disorder. It is characterized by congenital ataxia, hypotonia, developmental delay and at least one of the following features: neonatal respiratory disturbances and abnormal eye movements; including nystagmus and oculomotor apraxia. Molar tooth appearance is an essential finding for the diagnosis of Joubert syndrome. Read More

Front Hum Neurosci 2016 9;10:399. Epub 2016 Aug 9.

Cognitive Neurology and Aphasia Unit and Cathedra ARPA of Aphasia, Centro de Investigaciones Médico-Sanitarias, Instituto de Investigación Biomédica de Málaga (IBIMA), University of MalagaMalaga, Spain; Department of Psychobiology and Methodology of Behavioural Sciences, Faculty of Psychology, University of MalagaMalaga, Spain.

Foreign accent syndrome (FAS) is a speech disorder that is defined by the emergence of a peculiar manner of articulation and intonation which is perceived as foreign. In most cases of acquired FAS (AFAS) the new accent is secondary to small focal lesions involving components of the bilaterally distributed neural network for speech production. In the past few years FAS has also been described in different psychiatric conditions (conversion disorder, bipolar disorder, and schizophrenia) as well as in developmental disorders (specific language impairment, apraxia of speech). Read More

Tremor Other Hyperkinet Mov (N Y) 2016 16;6:368. Epub 2016 Jul 16.

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Background: The autosomal recessive ataxias are a heterogeneous group of disorders that are characterized by complex neurological features in addition to progressive ataxia. Hyperkinetic movement disorders occur in a significant proportion of patients, and may sometimes be the presenting motor symptom. Presentations with involuntary movements rather than ataxia are diagnostically challenging, and are likely under-recognized. Read More

Cerebellum 2016 10;15(5):636-40

Department of Neurology and Clinical Neuroscience, Karolinska University Hospital and Karolinska Institutet, 141 86, Stockholm, Sweden.

Premutations in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR1-related primary ovarian insufficiency (POI). Female FMR1 premutation carriers rarely develop motor features. Dual pathology is an emerging phenomenon among FMR1 premutation carriers. Read More

Dement Geriatr Cogn Dis Extra 2016 Jan-Apr;6(1):133-41. Epub 2016 Apr 15.

Department of Neurology, Faculty of Medicine, Oita University, Yufu, Japan.

Background: Brain perfusion may differ between patients with corticobasal syndrome (CBS) with and without aphasia.

Methods: Twenty-six (9 males and 17 females; mean age 76 ± 5.3 years) patients with CBS were enrolled in the study. Read More

Ophthalmic Genet 2017 Jan-Feb;38(1):88-90. Epub 2016 Apr 7.

a Department of Ophthalmology and Visual Sciences , University of Alberta , Edmonton , Alberta , Canada.

Dilated cardiomyopathy with ataxia syndrome (DCMA) is a rare mitochondrial condition associated with early onset cardiomyopathy and non-progressive ataxia. The cardiac manifestations may be progressive and often severe, resulting in significant morbidity and mortality. While optic nerve atrophy has been described in patients with DCMA, to our knowledge, there have been no reports of additional ocular phenotypes. Read More

Front Hum Neurosci 2016 10;10:65. Epub 2016 Mar 10.

Department of Language and Communication Science, City University LondonLondon, UK; Computational Linguistics and Psycholinguistics Research Center, Universiteit AntwerpenAntwerp, Belgium.

This paper presents the case of a 17-year-old right-handed Belgian boy with developmental FAS and comorbid developmental apraxia of speech (DAS). Extensive neuropsychological and neurolinguistic investigations demonstrated a normal IQ but impaired planning (visuo-constructional dyspraxia). A Tc-99m-ECD SPECT revealed a significant hypoperfusion in the prefrontal and medial frontal regions, as well as in the lateral temporal regions. Read More

BMC Neurol 2016 Mar 12;16:35. Epub 2016 Mar 12.

Department of Genetics, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia.

Background: In addition to its role in cell adhesion and gene expression in the canonical Wingless/integrated Wnt signaling pathway, β-catenin also regulates genes that underlie the transmission of nerve impulses. Mutations of CTNNB1 (β-catenin) have recently been described in patients with a wide range of neurodevelopmental disorders (intellectual disability, microcephaly and other syndromic features). We for the first time associate CTNNB1 mutation with hyperekplexia identifying it as an additional candidate for consideration in patients with startle syndrome. Read More

Brain Cogn 2016 Apr 27;104:48-57. Epub 2016 Feb 27.

University of Florida College of Medicine, Department of Neurology, Room L3-100, McKnight Brain Institute, 1149 Newell Drive, Gainesville, FL 32611, United States. Electronic address:

Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Read More

Eur J Paediatr Neurol 2016 Mar 18;20(2):286-295. Epub 2015 Dec 18.

Manchester Centre for Genomic Medicine, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK. Electronic address:

Introduction: Next Generation Sequencing (NGS) is a useful tool in diagnosis of rare disorders but the interpretation of data can be challenging in clinical settings. We present results of extended studies on a family of multiple members with global developmental delay and learning disability, where another research group postulated the underlying cause to be a homozygous RABL6 missense variant.

Methods And Results: Using data from the Exome Variant Server, we show that missense RABL6 variants are unlikely to cause early onset rare developmental disorder. Read More

Cortex 2016 Jan 14;74:149-57. Epub 2015 Nov 14.

Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. Read More

Front Neurol 2015 12;6:209. Epub 2015 Oct 12.

Klinik für Neurologie, Kantonsspital St. Gallen , St. Gallen , Switzerland.

Background: Both the supplementary motor complex (SMC), consisting of the supplementary motor area (SMA) proper, the pre-SMA, and the supplementary eye field, and the rostral cingulate cortex are supplied by the anterior cerebral artery (ACA) and are involved in higher motor control. The Bereitschaftspotential (BP) originates from the SMC and reflects cognitive preparation processes before volitional movements. ACA strokes may lead to impaired motor control in the absence of limb weakness and evoke an alien hand syndrome (AHS) in its extreme form. Read More

Brain Behav 2015 Oct 16;5(10):e00371. Epub 2015 Sep 16.

Department of Sport and Health Sciences Institute of Human Movement Science Technische Universität München München Germany.

Background And Purpose: A large body of research reports that stroke patients are debilitated in terms of daily independence after dismissal from the hospital unit. Patients struggle with the use of daily objects or performing complex actions. Differences between individual deficits of patients are often associated with the site of the brain damage. Read More

J Clin Exp Neuropsychol 2015 4;37(10):1062-73. Epub 2015 Sep 4.

a Brain Rehabilitation Research Center of the Malcom Randall VAMC , Gainesville , FL , USA.

Background/objectives: In most right-handed people, the left hemisphere is dominant for programming the temporal and spatial "how" (praxis) aspects of purposeful skilled movements, and the right hemisphere is dominant for control of the intentional "when" aspects of actions that mediate initiation, persistence, termination, and inhibition. Since the interhemispheric axons of the corpus callosum are especially susceptible to shearing from torsional forces during traumatic brain injury (TBI), the goal of this study was to learn whether participants with a history of severe traumatic brain injury demonstrate three types of cognitive-motor impairments that may result from callosal injury: ideomotor apraxia of the left hand, limb kinetic apraxia of the left hand, and hypokinesia of the right hand in response to left hemispatial stimuli.

Method: Nine participants with severe TBI and nine healthy control participants were studied for the presence of ideomotor apraxia, limb kinetic apraxia, and hypokinesia. Read More

Neurophysiol Clin 2014 Nov 10;44(5):457-69. Epub 2014 Sep 10.

Tilburg University, Department of Psychology, Tilburg, The Netherlands.

Background: Auditory stimulation is often used to evoke responses in unresponsive patients who have suffered severe brain injury. In order to investigate visual responses, we examined visual evoked potentials (VEPs) and behavioral responses to visual stimuli in vegetative patients during recovery to consciousness.

Methods: Behavioral responses to visual stimuli (visual localization, comprehension of written commands, and object manipulation) and flash VEPs were repeatedly examined in eleven vegetative patients every two weeks for an average period of 2. Read More

Cerebellum 2015 Feb;14(1):39-42

Clinical and Experimental Neurolinguistics, CLIN, Vrije Universiteit Brussel, Brussels, Belgium,

As early as the beginning of the nineteenth century, a variety of nonmotor cognitive and affective impairments associated with cerebellar pathology were occasionally documented. A causal link between cerebellar disease and nonmotor cognitive and affective disorders has, however, been dismissed for almost two centuries. During the past decades, the prevailing view of the cerebellum as a mere coordinator of autonomic and somatic motor function has changed fundamentally. Read More

PLoS One 2014 30;9(10):e110326. Epub 2014 Oct 30.

Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.

Background: Corticobasal Syndrome (CBS) is a rare neurodegenerative syndrome characterized by unilaterally beginning frontoparietal and basal ganglia atrophy. The study aimed to prove the hypothesis that there are differences in hemispheric susceptibility to disease-related changes.

Methods: Two groups of CBS patients with symptoms starting either on the left or right body side were investigated. Read More

Neurol Clin Pract 2014 Aug;4(4):304-312

Department of Neurology (LMC, MG, RGG), University of Pennsylvania, Philadelphia; Department of Neurology (TR), University of Chicago, IL; and Department of Internal Medicine and Pathology (JJR), American University of Beirut, Lebanon.

Corticobasal syndrome (CBS) is characterized by asymmetric involuntary movements including rigidity, tremor, dystonia, and myoclonus, and often associated with apraxia, cortical sensory deficits, and alien limb phenomena. Additionally, there are various nonmotor (cognitive and language) deficits. CBS is associated with several distinct histopathologies, including corticobasal degeneration, other forms of tau-related frontotemporal lobar degeneration such as progressive supranuclear palsy, and Alzheimer disease. Read More

Curr Treat Options Neurol 2014 Nov;16(11):319

Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94115, USA,

Opinion Statement: Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative diseases with heterogeneous clinical presentations and two predominant types of underlying neuropathology. FTD typically comprises three distinct clinical syndromes: behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), and nonfluent variant primary progressive aphasia (nfvPPA). FTD also frequently overlaps both clinically and neuropathologically with three other neurodegenerative syndromes: corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS). Read More

Brain 2014 Oct 11;137(Pt 10):2783-95. Epub 2014 Aug 11.

6 Department of Radiology (Neuroradiology), Mayo Clinic, Rochester, MN 55905, USA.

Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2. Read More

J Inherit Metab Dis 2015 Jan 5;38(1):145-56. Epub 2014 Aug 5.

Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Via Giustiniani 3, Padova, 35128, Italy.

Coenzyme Q(10) is a remarkable lipid involved in many cellular processes such as energy production through the mitochondrial respiratory chain (RC), beta-oxidation of fatty acids, and pyrimidine biosynthesis, but it is also one of the main cellular antioxidants. Its biosynthesis is still incompletely characterized and requires at least 15 genes. Mutations in eight of them (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) cause primary CoQ(10) deficiency, a heterogeneous group of disorders with variable age of onset (from birth to the seventh decade) and associated clinical phenotypes, ranging from a fatal multisystem disease to isolated steroid resistant nephrotic syndrome (SRNS) or isolated central nervous system disease. Read More

Mult Scler 2014 Sep 1;20(10):1413-6. Epub 2014 Jul 1.

Division of Neurology, Asahikawa Medical University, Japan.

A woman with Sjögren syndrome manifesting as aphasia with a left deep cerebral white matter lesion tested positive for anti-aquaporin 4 (AQP4) antibody. Open biopsy of the lesion revealed active demyelination with edematous changes and the preservation of most axons, indicating a non-necrotic demyelinating lesion. Immunostaining for AQP4 was diffusely lost, whereas the loss of glial fibrillary acidic protein immunostaining was limited but with highly degenerated astrocytic foot processes in perivascular areas. Read More

Lancet Diabetes Endocrinol 2014 Aug 23;2(8):619-26. Epub 2014 Jun 23.

University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address:

Background: The thyroid hormone receptor α gene (THRA) transcript is alternatively spliced to generate either thyroid hormone receptor (TR)α1 or a non-hormone-binding variant protein, TRα2, the function of which is unknown. Here, we describe the first patients identified with a mutation in THRA that affects both TRα1 and TRα2, and compare them with patients who have resistance to thyroid hormone owing to a mutation affecting only TRα1, to delineate the relative roles of TRα1 and TRα2.

Methods: We did clinical, biochemical, and genetic analyses of an index case and her two sons. Read More

Mol Genet Metab Rep 2014 10;1:223-231. Epub 2014 May 10.

Metabolic Unit, Department of Medical Genetics, CHU-CHC, Liège, Belgium.

A 1-year-old girl born to consanguineous parents presented with unexplained liver failure, leading to transplantation at 19 months. Subsequent partial splenectomy for persistent cytopenia showed the presence of foamy cells, and Gaucher disease was confirmed by homozygosity for the p.Leu483Pro mutation in the gene. Read More

Parkinsonism Relat Disord 2014 Jul 13;20(7):748-54. Epub 2014 Apr 13.

Division of Neurology, Department of Clinical Sciences, Lund University, Sweden; Department for Neurology, Skåne University Hospital, Sweden. Electronic address:

Background: We describe the clinical characteristics of a Swedish family with autosomal dominant cerebellar ataxia, sensory and autonomic neuropathy, additional neurological features and unknown genetic cause.

Methods: Fourteen affected family members were identified. Their disorder was characterized by neurological examination, MRI, electroneurography, electromyography, MIBG-scintigraphy, and tilt-testing. Read More

Hum Mol Genet 2014 Sep 23;23(18):4758-69. Epub 2014 Apr 23.

Program in Neurogenetics, Department of Neurology and Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.

Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional role of senataxin in disease, we examined differential gene expression in AOA2 patient fibroblasts, identifying a core set of genes showing altered expression by microarray and RNA-sequencing. Read More

Hum Genome Var 2014 6;1:14020. Epub 2014 Nov 6.

Department of Paediatrics, College of Medicine and Heath Sciences, United Arab Emirates University , Al-Ain, United Arab Emirates.

Joubert syndrome (JS) is a rare autosomal recessive (AR), neurological condition characterized by dysgenesis of the cerebellar vermis with the radiological hallmark of molar tooth sign, oculomotor apraxia, recurrent hyperventilation and intellectual disability. Most cases display a broad spectrum of additional features, including polydactyly, retinal dystrophy and renal abnormalities, which define different subtypes of JS-related disorders (JSRDs). To date, 23 genes have been shown to cause JSRDs, and although most of the identified genes encode proteins involved in cilia function or assembly, the molecular mechanisms associated with ciliary signaling remain enigmatic. Read More

Brain 2014 Jan 29;137(Pt 1):208-20. Epub 2013 Nov 29.

1 Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0SZ, UK.

The volitional impairments of alien limb and apraxia are a defining feature of the corticobasal syndrome, but a limited understanding of their neurocognitive aetiology has hampered progress towards effective treatments. Here we combined several key methods to investigate the mechanism of impairments in voluntary action in corticobasal syndrome. We used a quantitative measure of awareness of action that is based on well-defined processes of motor control; structural and functional anatomical information; and evaluation against the clinical volitional disorders of corticobasal syndrome. Read More

Cerebellum 2014 Feb;13(1):79-88

Department of Pediatric Neurology, University Children's Hospital of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.

Cerebellar cysts are rare findings in pediatric neuroimaging and rather characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim to report on seven children with cerebellar cysts showing absence of weakness and ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about neurological and ophthalmological features, outcome, and creatine kinase values were collected from clinical histories and follow-up examinations. Read More

Brain Inj 2013 2;27(11):1256-62. Epub 2013 Aug 2.

School of Health Sciences and Social Care, Brunel University, Uxbridge , Middlesex , UK .

Primary Objective: Research has shown that traumatic brain injury (TBI) can affect a person's ability to perform previously learned skills. Dysexecutive syndrome and inattention, for example, alongside a number of other cognitive and behavioural impairments such as memory loss and lack of motivation, significantly affect day-to-day functioning following TBI. This study examined the efficacy of video modelling in emerging speech in an adult male with TBI caused by an assault. Read More

Mech Ageing Dev 2013 Oct 9;134(10):496-505. Epub 2013 Apr 9.

The David and Inez Myers Laboratory for Cancer Genetics, Department of Human Molecular Genetics and Biochemistry, Tel Aviv 69978, Israel.

The cerebellum is exquisitely sensitive to deficiencies in the cellular response to specific DNA lesions. Genetic disorders caused by such deficiencies involve relentless, progressive cerebellar atrophy with striking loss of Purkinje and granule neurons. The reason for the extreme sensitivity of these cells to defective response to certain DNA lesions is unclear. Read More

J Neurol 2013 Jul 10;260(7):1880-8. Epub 2013 Apr 10.

Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.

Alien limb phenomenon refers to involuntary motor activity of a limb in conjunction with the feeling of estrangement from that limb. Alien limb serves as a diagnostic feature of corticobasal syndrome. Our objective was to determine the differential diagnoses of alien limb and to determine the features in a large group of patients with the alien limb with different underlying etiologies. Read More

Can J Neurol Sci 2013 Mar;40(2):235-40

Section of Pediatric Neurology, University of Manitoba, Winnipeg, Manitoba, Canada.

Introduction: Infantile-onset saccade initiation delay (ISID), also known as congenital ocular motor apraxia, is characterized by the inability to initiate volitional horizontal saccades. Other abnormalities including developmental delay and ataxia have been reported. The frequency of these abnormalities is unknown. Read More

Brain Nerve 2013 Jan;65(1):19-30

Department of Clinical Neurology and Stroke Medicine, Yokohama City University, Japan.

Corticobasal syndrome (CBS) is a clinical syndrome presenting with progressive asymmetric bradykinesia, rigidity, and dystonia accompanied by cortical signs, such as apraxia, alien limb phenomena, cortical sensory loss, myoclonus, and mirror movements. CBS is associated with different pathological conditions including FTLD-tau (corticobasal degeneration, CBD; progressive supranuclear palsy, PSP: and Pick disease), FTLD-TDP, Alzheimer disease, Creutzfeldt-Jakob disease, and Parkinson disease/dementia with Lewy bodies. Among these, the most common pathology is CBD. Read More

Rinsho Shinkeigaku 2012 ;52(11):1224-7

Graduate school of Health Sciences, Hokkaido University.

FTLD consists of three clinical types: behavioural variant FTD, progressive non-fluent aphasia (PNFA) and semantic dementia (SD). The latter two types manifest aphasia. Thus, it is quite important to pertinently assess the symptoms of aphasia and related impairments for diagnosis of FTLD. Read More

J Alzheimers Dis 2013 ;33 Suppl 1:S211-7

Neuroscience Research Australia and University of New South Wales, Randwick, NSW, Austarlia.

This review focuses on six key papers published in the mid 2000 s based on work conducted in Cambridge. The first two relate to clinico-pathological studies which established that Alzheimer's disease (AD) is a relatively common cause of focal cortical syndromes, notably progressive aphasia (largely nonfluent), progressive apraxia, and posterior cortical atrophy with complex visual symptoms. Building on these findings, criteria for the progressive aphasias have been developed which define the variant associated with AD (progressive logopenic aphasia). Read More