Zhaleh Khaleeli

University College London

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Alan J. Thompson

National Hospital for Neurology and Neurosurgery

Olga Ciccarelli

University College London

Mara Cercignani

Brighton and Sussex Medical School

Xavier Montalbán

Vall d'Hebron Institut de Recerca

Jaume Sastre‐Garriga

Universitat Autònoma de Barcelona

Frederik Barkhof

Amsterdam UMC Location VUmc

Massimo Filippi

Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele

ÀR

Àlex Rovira

Vall d'Hebron Hospital Universitari

David H. Miller

University College London

D. H. Miller

Purdue University West Lafayette

Cooperative Institutions

University College London

139

National Hospital for Neurology and Neurosurgery

104

Queen Mary University of London

Royal London Hospital

University College London Hospitals NHS Foundation Trust

National Institute for Health Research

Amsterdam UMC Location VUmc

National Health Service

Barts Health NHS Trust

Moorfields Eye Hospital

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WHY NEUROLOGY? THE CAREER CHOICES OF CURRENT UK NEUROLOGY TRAINEES

Journal of Neurology Neurosurgery & Psychiatry (2015)

Rhys H. Thomas Helen Devine Ann Donnelly Alexander Foulkes Clare Galtrey

Introduction It is important that we attract high-calibre medics to neurology. There are few studies of what motivated neurologists to choose their speciality, when they chose, or what else they might have become. Methods All UK neurology trainees were invited to complete an online survey. Results 160 trainees responded (53% female; 17% less-than-fulltime). 54% decided on neurology before graduating (6% before medical school), whilst 29% decided after foundation training. Common reasons to choose neurology included: academically interesting (72%); clinical exposure as a student or junior (67%); personality fit (53%); influential role-model (37%). Less common motivations included lifestyle, family friendliness, prestige, and family members with neurological conditions. Two trainees chose neurology because they personally have a neurological condition. When asked what their second choice of medical career would have been the answers were diverse and 31 different specialties were named, but only one might have been a neurosurgeon. Conclusions Careers advice should begin early in medical school and continue through medical training with direct exposure to clinical neurology. Traditional neurology values such as the intellectual challenge should be emphasised. Neurologists have a broad interest in medical and psychiatric specialties underlining the importance of core medical training to developing neurologists of the future.

Clinical neurology

Specialty

10.1136/jnnp-2015-312379.42

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Citations (2)

Corpus callosum damage predicts disability progression and cognitive dysfunction in primary‐progressive MS after five years

Human Brain Mapping (2012)

Benedetta Bodini Mara Cercignani Zhaleh Khaleeli David H. Miller María A. Ron

We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability.

Splenium

10.1002/hbm.21499

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Citations (57)

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Therapeutic Advances in Neurological Disorders (2021)

Kimberley Allen‐Philbey Stefania De Trane Zhifeng Mao César Álvarez-González Joela Mathews

To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients.Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3-4 days during week 1. Based on lymphocyte count at week 4, patients received another 0-3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts.In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17-72) years and EDSS 0-8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months.Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

Cladribine

Mitoxantrone

10.1177/17562864211057661

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Citations (7)

Primary progressive multiple sclerosis diagnostic criteria: a reappraisal

Multiple Sclerosis Journal (2009)

Xavier Montalbán Jaume Sastre‐Garriga Massimo Filippi Zhaleh Khaleeli N. Téllez

The diagnostic criteria used in primary progressive (PP) and relapsing—remitting (RR) multiple sclerosis (MS) show substantial differences. This introduces complexity in the diagnosis of MS which could be resolved if these criteria could be unified in terms of the requirements for dissemination in space (DIS). The aim of this study was to assess whether a single algorithm may be used to demonstrate DIS in all forms of MS. Five sets of RRMS criteria for DIS were applied to a cohort of 145 patients with established PPMS (mean disease duration: 11 years — PPMS-1): C1: Barkhof—Tintoré (as in 2005 McDonald’s criteria); C2: Swanton et al. (as in JNNP 2006); C3: presence of oligoclonal bands plus two lesions (as in McDonald’s criteria); C4 and C5: a two-step approach was also followed (patients not fulfilling C1 or C2 were then assessed for C3). Two sets of PPMS criteria for DIS were applied: C6: Thompson et al. (as in 2001 McDonald’s criteria); C7: 2005 McDonald criteria. A second sample of 55 patients with less than 5 years of disease duration (PPMS-2) was also analysed using an identical approach. For PPMS-1/PPMS-2, fulfilment was: C1:73.8%/66.7%; C2:72.1%/59.3%; C3:89%/79.2%; C4:96%/92.3%; C5:96%/85.7%; C6:85.8%/78.7%; C7:91%/80.4%. Levels of fulfilment suggest that the use of a single set of criteria for DIS in RRMS and PPMS might be feasible, and reinforce the added value of cerebrospinal fluid (CSF) findings to increase fulfilment in PPMS. Unification of the DIS criteria for both RRMS and PPMS could be considered in further revisions of the MS diagnostic criteria.

Relapsing remitting

McDonald criteria

Clinically isolated syndrome

10.1177/1352458509348422

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Citations (44)

Brain atrophy in MS: long-term prognostic value

Multiple Sclerosis Journal (2011)

Veronica Popescu Federica Agosta Hanneke E. Hulst Ingrid C. Sluimer D.L. Knol

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Clinical relevance of cortical network dynamics in early primary progressive MS

Multiple Sclerosis Journal (2019)

Carmen Tur Baris Kanber Arman Eshaghi Dan Altmann Zhaleh Khaleeli

Background: Structural cortical networks (SCNs) reflect the covariance between the cortical thickness of different brain regions, which may share common functions and a common developmental evolution. SCNs appear abnormal in neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases, but have never been assessed in primary progressive multiple sclerosis (PPMS). Objective: The aim of this study was to test whether SCNs are abnormal in early PPMS and change over 5 years, and correlate with disability worsening. Methods: A total of 29 PPMS patients and 13 healthy controls underwent clinical and brain magnetic resonance imaging (MRI) assessments for 5 years. Baseline and 5-year follow-up cortical thickness values were obtained and used to build correlation matrices, considered as weighted graphs to obtain network metrics. Bootstrap-based statistics assessed SCN differences between patients and controls and between patients with fast and slow progression. Results: At baseline, patients showed features of lower connectivity ( p = 0.02) and efficiency ( p < 0.001) than controls. Over 5 years, patients, especially those with fastest clinical progression, showed significant changes suggesting an increase in network connectivity ( p < 0.001) and efficiency ( p < 0.02), not observed in controls. Conclusion: SCNs are abnormal in early PPMS. Longitudinal SCN changes demonstrated a switch from low- to high-efficiency networks especially among fast progressors, indicating their clinical relevance.

Clinical Significance

10.1177/1352458519831400

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Citations (15)

Magnetization Transfer Ratio in Gray Matter

Archives of Neurology (2008)

Zhaleh Khaleeli Daniel R. Altmann Mara Cercignani Olga Ciccarelli David H. Miller

Magnetization transfer imaging has the potential to provide a surrogate marker for progression in primary progressive multiple sclerosis (PPMS).To investigate whether brain magnetization transfer imaging, T2 lesion load, and atrophy changes over 3 years reflect concurrent clinical changes, and which baseline imaging measure best predicts progression over 3 years in early PPMS.Prospective study.National Hospital for Neurology and Neurosurgery and the Institute of Neurology, London, England.Forty-seven patients with PPMS (of whom 43 completed the study) and 18 control subjects.Brain magnetization transfer imaging (including T2-weighted images) and volume sequences every 6 months for 3 years.Changes in Expanded Disability Status Scale (EDSS) score and associations with rate of change in imaging variables.More rapid decline in gray matter mean and peak location magnetization transfer ratio and T2 lesion load increase were associated with greater rates of progression on the EDSS. Baseline gray matter peak height magnetization transfer ratio best predicted progression over 3 years.Gray matter magnetization transfer ratio meets many of the criteria for a surrogate marker of progression in early PPMS.

Magnetization transfer

Neuroradiology

10.1001/archneur.65.11.1454

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Citations (60)

Dynamics and Treatment Response of Compartmentalised Sarcoidosis Using Longitudinal High Resolution Retinal Optical Coherence Tomography

Journal of the Foundations of Ophthalmology (2023)

Anastasia Margariti Victoria Nowak Fion Bremner Zhaleh Khaleeli Axel Petzold

10.48089/jfo7688154

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Citations (0)

Brain atrophy and lesion load predict long term disability in multiple sclerosis

Journal of Neurology Neurosurgery & Psychiatry (2013)

Veronica Popescu Federica Agosta Hanneke E. Hulst Ingrid C. Sluimer Dirk L. Knol

Objective

To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS).

Design

From eight MAGNIMS (MAGNetic resonance Imaging in MS) centres, we retrospectively included 261 MS patients with MR imaging at baseline and after 1–2 years, and Expanded Disability Status Scale (EDSS) scoring at baseline and after 10 years. Annualised whole brain atrophy, central brain atrophy rates and T2 lesion volumes were calculated. Patients were categorised by baseline diagnosis as primary progressive MS (n=77), clinically isolated syndromes (n=18), relapsing–remitting MS (n=97) and secondary progressive MS (n=69). Relapse onset patients were classified as minimally impaired (EDSS=0–3.5, n=111) or moderately impaired (EDSS=4–6, n=55) according to their baseline disability (and regardless of disease type). Linear regression models tested whether whole brain and central atrophy, lesion volumes at baseline, follow-up and lesion volume change predicted 10 year EDSS and MS Severity Scale scores.

Results

In the whole patient group, whole brain and central atrophy predicted EDSS at 10 years, corrected for imaging protocol, baseline EDSS and disease modifying treatment. The combined model with central atrophy and lesion volume change as MRI predictors predicted 10 year EDSS with R²=0.74 in the whole group and R²=0.72 in the relapse onset group. In subgroups, central atrophy was predictive in the minimally impaired relapse onset patients (R²=0.68), lesion volumes in moderately impaired relapse onset patients (R²=0.21) and whole brain atrophy in primary progressive MS (R²=0.34).

Conclusions

This large multicentre study points to the complementary predictive value of atrophy and lesion volumes for predicting long term disability in MS.

10.1136/jnnp-2012-304094

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Citations (304)

HLA-DRB1*15 influences the development of brain tissue damage in early PPMS

Neurology (2014)

Carmen Tur Sreeram V Ramagopalan Daniel R. Altmann Benedetta Bodini Mara Cercignani

To investigate whether (1) there were differences between HLA-DRB1*15-positive and -negative patients at baseline, and (2) HLA-DRB1*15-positive patients showed a greater development of brain and spinal cord damage, as assessed by MRI, and greater progression of disability, during a 5-year follow-up, compared with HLA-DRB1*15-negative patients.HLA-DRB1*15 typing was performed in 41 patients with primary progressive multiple sclerosis (PPMS) who were recruited within 5 years of symptom onset. All patients and 18 healthy controls were studied clinically and with MRI at baseline, and every 6 months for 3 years, and then at 5 years. Magnetization transfer ratio parameters and volumes for brain gray matter and normal-appearing white matter, brain T2 lesion load, and spinal cord cross-sectional area were obtained. Patient disability was assessed at each visit using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite subscores.There were no significant differences between HLA-DRB1*15-positive and -negative patients at baseline. HLA-DRB1*15-positive patients showed a greater decline in brain magnetization transfer ratio for gray matter and normal-appearing white matter (both p = 0.005) than HLA-DRB1*15-negative patients over 5 years, while the same parameters did not change over time in healthy controls. HLA-DRB1*15-positive patients also showed a trend toward a faster increase in brain T2 lesion load than HLA-DRB1*15-negative patients (0.29 [95% confidence interval 0.20-0.38] vs 0.21 [0.13-0.30] mL/mo, p = 0.085) and higher T2 lesion volumes at all time points (average difference [95% confidence interval]: 10.58 mL [7.09-14.07], p < 0.001) during the follow-up, after adjusting for disease duration.These findings suggest that HLA-DRB1*15 influences the progression of brain pathology in PPMS.

HLA-DRB1

Brain damage

Grey matter

10.1212/wnl.0000000000000959

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Citations (20)