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Article ; Online: Strachan's syndrome and riboflavin deficiency.

Kramarz, Caroline / McHugh, James / Rossor, Alexander

2024 Volume 24, Issue 2, Page(s) 121–128

Abstract: Strachan's syndrome comprises a triad of optic, auditory and painful sensory peripheral neuropathy. It has been recognised since the late 19th century and is presumed to result from nutritional deficiency. Patients present acute or subacutely after a ... ...

Abstract	Strachan's syndrome comprises a triad of optic, auditory and painful sensory peripheral neuropathy. It has been recognised since the late 19th century and is presumed to result from nutritional deficiency. Patients present acute or subacutely after a period of systemic illness, weight loss or, most commonly, dietary restriction, especially veganism, which can cause riboflavin (vitamin B
MeSH term(s)	Humans ; Peripheral Nervous System Diseases ; Riboflavin Deficiency ; Optic Nerve Diseases ; Riboflavin/therapeutic use ; Vitamins ; Vitamin B 12 Deficiency
Chemical Substances	Riboflavin (TLM2976OFR) ; Vitamins
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2170881-2
ISSN	1474-7766 ; 1474-7758
ISSN (online)	1474-7766
ISSN	1474-7758
DOI	10.1136/pn-2023-003822
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Article ; Online: Are we prepared for clinical trials in Charcot-Marie-Tooth disease?

Rossor, A M / Shy, M E / Reilly, M M

Brain research

2019 Volume 1729, Page(s) 146625

Abstract: There has been considerable progress in developing treatments for Charcot-Marie-Tooth disease with a number of therapies either completing or nearing clinical trials. In the case of CMT1A, the commonest subtype of CMT, there have been more than five ... ...

Abstract	There has been considerable progress in developing treatments for Charcot-Marie-Tooth disease with a number of therapies either completing or nearing clinical trials. In the case of CMT1A, the commonest subtype of CMT, there have been more than five randomised, double blind placebo-controlled trials. Although these trials were negative for the primary outcome measure, considerable lessons have been learnt leading to the collection of large prospective natural history data sets with which to inform future trial design as well as the development of new and sensitive outcome measures. In this review we summarise the difficulties of conducting clinical trials in a slowly progressive disease such as CMT1A and the requirement for sensitive, reproducible and clinically relevant outcome measures. We summarise the current array of CMT specific outcome measures subdivided into clinical outcome measures, functional outcome measures, patient reported outcome measures, biomarkers of disease burden and treatment specific biomarkers of target engagement. Although there is now an array of CMT specific outcome measures, which collectively incorporate clinically relevant, sensitive and reproducible outputs, a single outcome measure incorporating all three qualities remains elusive.
MeSH term(s)	Biomarkers/analysis ; Charcot-Marie-Tooth Disease/therapy ; Clinical Trials as Topic ; Humans ; Outcome Assessment, Health Care
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-12-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2019.146625
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Article ; Online: An approach to assessing immunoglobulin dependence in chronic inflammatory demyelinating inflammatory polyneuropathy.

Kapoor, Mahima / Compton, Laura / Rossor, Alex / Hutton, Elsbeth / Manji, Hadi / Lunn, Mike / Reilly, Mary / Carr, Aisling

Journal of the peripheral nervous system : JPNS

2021 Volume 26, Issue 4, Page(s) 461–468

Abstract: Regular immunoglobulin treatment maintains strength and prevents disability in chronic inflammatory demyelinating polyneuropathy (CIDP). Discrimination between active disease, with optimum symptom control on treatment, and disease in remission not ... ...

Abstract	Regular immunoglobulin treatment maintains strength and prevents disability in chronic inflammatory demyelinating polyneuropathy (CIDP). Discrimination between active disease, with optimum symptom control on treatment, and disease in remission not requiring treatment is essential for therapeutic decision-making and clinical trial design. To compare treatment cessation versus gradual dose reduction in assessment of disease activity (immunoglobulin dependence) in a cohort of stable CIDP patients on maintenance immunoglobulin treatment. An approach to restabilization of immunoglobulin-dependent individuals is also described. Retrospective review of IVIg cessation or gradual reduction in 33 patients with stable CIDP on maintenance IVIg. Demographic, clinical and treatment data were collected; clinical monitoring data were recorded prospectively as part of routine clinical practice. A total of 21/33 patients (62.6%) were immunoglobulin dependent, (gradual dose reduction:11, cessation:10). Mean change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) (-15, standard deviation [SD] 16) and Medical Research Council Sum Score (MRC-SS) (-4, SD: 4) was clinically and statistically meaningful (>75% exceeded minimum clinically important differences). Mean time to deterioration was 5.0 (SD: 4.6) months, shorter in cessation group (3.5 months) than gradual reduction group (8.8 months). All patients were restabilized to previous baseline (M: 2.3, SD: 4.3 months), half within 1 week of retreatment. A total of 12 patients (37.4%) remained stable without treatment for ≥2 years (remission). A total of 50% were identified rapidly by cessation and 50% by gradual dose reduction requiring mean 4.8 (SD: 2.8) years follow-up and costing £113 623 per person Ig spend. No predictors of disease activity were identified. A treatment cessation trial with close clinical monitoring is an efficient, cost-effective and safe approach to assessing disease activity in CIDP.
MeSH term(s)	Cohort Studies ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Minimal Clinically Important Difference ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/drug therapy ; Retrospective Studies
Chemical Substances	Immunoglobulins, Intravenous
Language	English
Publishing date	2021-10-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1364009-4
ISSN	1529-8027 ; 1085-9489
ISSN (online)	1529-8027
ISSN	1085-9489
DOI	10.1111/jns.12470
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Zs.A 5106: Show issues

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Article ; Online: Biallelic Loss-of-Function Variants in

Hirsch, Yoel / Chung, Wendy K / Novoselov, Sergey / Weimer, Louis H / Rossor, Alexander / LeDuc, Charles A / McPartland, Amanda J / Cabrera, Ernesto / Ekstein, Josef / Scher, Sholem / Nelson, Rick F / Schiavo, Giampietro / Henderson, Lindsay B / Booth, Kevin T A

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of ... ...

Abstract	Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the
MeSH term(s)	Humans ; Adaptor Proteins, Signal Transducing/genetics ; Cytoskeletal Proteins/genetics ; Deafness/genetics ; Hearing Loss/genetics ; Pedigree ; Peripheral Nervous System Diseases/genetics ; Phenotype
Chemical Substances	Adaptor Proteins, Signal Transducing ; BICD1 protein, human ; Cytoskeletal Proteins
Language	English
Publishing date	2023-05-17
Publishing country	Switzerland
Document type	Case Reports ; Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24108897
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Article ; Online: Association of plasma neurofilament light chain with disease activity in chronic inflammatory demyelinating polyradiculoneuropathy.

Kapoor, Mahima / Carr, Aisling / Foiani, Martha / Heslegrave, Amanda / Zetterberg, Henrik / Malaspina, Andrea / Compton, Laura / Hutton, Elspeth / Rossor, Alexander / Reilly, Mary M / Lunn, Michael P

European journal of neurology

2022 Volume 29, Issue 11, Page(s) 3347–3357

Abstract: Background and purpose: This study was undertaken to explore associations between plasma neurofilament light chain (pNfL) concentration (pg/ml) and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and ... ...

Abstract	Background and purpose: This study was undertaken to explore associations between plasma neurofilament light chain (pNfL) concentration (pg/ml) and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and examine the usefulness of pNfL concentrations in determining disease remission. Methods: We examined pNfL concentrations in treatment-naïve CIDP patients (n = 10) before and after intravenous immunoglobulin (IVIg) induction treatment, in pNfL concentrations in patients on maintenance IVIg treatment who had stable (n = 15) versus unstable disease (n = 9), and in clinically stable IVIg-treated patients (n = 10) in whom we suspended IVIg to determine disease activity and ongoing need for maintenance IVIg. pNfL concentrations in an age-matched healthy control group were measured for comparison. Results: Among treatment-naïve patients, pNfL concentration was higher in patients before IVIg treatment than healthy controls and subsequently reduced to be comparable to control group values after IVIg induction. Among CIDP patients on IVIg treatment, pNfL concentration was significantly higher in unstable patients than stable patients. A pNFL concentration > 16.6 pg/ml distinguished unstable treated CIDP from stable treated CIDP (sensitivity = 86.7%, specificity = 66.7%, area under receiver operating characteristic curve = 0.73). Among the treatment withdrawal group, there was a statistically significant correlation between pNfL concentration at time of IVIg withdrawal and the likelihood of relapse (r = 0.72, p < 0.05), suggesting an association of higher pNfL concentration with active disease. Conclusions: pNfL concentrations may be a sensitive, clinically useful biomarker in assessing subclinical disease activity.
MeSH term(s)	Biomarkers ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infusions, Intravenous ; Intermediate Filaments ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/drug therapy
Chemical Substances	Biomarkers ; Immunoglobulins, Intravenous
Language	English
Publishing date	2022-07-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15496
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Zs.A 4738: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Clinical spectrum, treatment and outcome of children with suspected diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy.

Silwal, A / Pitt, M / Phadke, R / Mankad, K / Davison, J E / Rossor, A / DeVile, C / Reilly, M M / Manzur, A Y / Muntoni, F / Munot, P

Neuromuscular disorders : NMD

2018 Volume 28, Issue 9, Page(s) 757–765

Abstract: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable chronic disorder of the peripheral nervous system. We retrospectively studied 30 children with a suspected diagnosis of CIDP. The diagnosis of CIDP was compared against the ... ...

Abstract	Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable chronic disorder of the peripheral nervous system. We retrospectively studied 30 children with a suspected diagnosis of CIDP. The diagnosis of CIDP was compared against the childhood CIDP revised diagnostic criteria 2000. Of the 30 children, five did not meet the criteria and four others met the criteria but subsequently had alternative diagnosis, leaving a total of 21 children (12 male) with CIDP as the final diagnosis. Thirteen children presented with chronic symptom-onset (>8 weeks). The majority presented with gait difficulties or pain in legs (n = 16). 12 children (57%) met the neurophysiological criteria and 18/19 (94%) met the cerebrospinal fluid criteria. Nerve biopsy was suggestive in 3/9 (33%), with magnetic resonance imaging supportive in 9/20 (45%). Twenty-one children received immuno-modulatory treatment at first presentation, of which majority (n = 19, 90%) received IVIG (immunoglobulin) monotherapy with 13 (68%) showing a good response. 8 children received second line treatment with either IVIG or steroids or plasmapharesis (PE) and 4 needed other immune-modulatory agents. During a median follow-up of 3.6 years, 9 (43%) had a monophasic course and 12 (57%) had a relapsing-remitting course. At last paediatric follow up 7 (33%) were off all treatment, 9 (43%) left with no or minimal residual disability and 6 (28%) children were walking with assistance (n = 3) or were non-ambulant (n = 3). Our review highlights challenges in the diagnosis and management of paediatric CIDP. It also confirms that certain metabolic disorders may mimic CIDP.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Disease Progression ; Female ; Gait/physiology ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Immunologic Factors/therapeutic use ; Magnetic Resonance Imaging ; Male ; Neural Conduction/physiology ; Plasmapheresis ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy ; Retrospective Studies ; Treatment Outcome
Chemical Substances	Immunoglobulins, Intravenous ; Immunologic Factors
Language	English
Publishing date	2018-06-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1077681-3
ISSN	1873-2364 ; 0960-8966
ISSN (online)	1873-2364
ISSN	0960-8966
DOI	10.1016/j.nmd.2018.06.001
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Article ; Online: Peripheral nerve neurolymphomatosis: Clinical features, treatment, and outcomes.

Keddie, Stephen / Nagendran, Arjuna / Cox, Tom / Bomsztyk, Joshua / Jaunmuktane, Zane / Brandner, Sebastian / Manji, Hadi / Rees, Jeremy H / Ramsay, Alan D / Rossor, Alexander / D'Sa, Shirley / Reilly, Mary M / Carr, Aisling S / Lunn, Michael P

Muscle & nerve

2020 Volume 62, Issue 5, Page(s) 617–625

Abstract: This series characterises nine patients with neurohistopathologically proven peripheral nerve neurolymphomatosis. A search of the hospital neuropathology database from 2002 to 2019 identified biopsy proven cases. Clinical data, investigation modalities, ... ...

Abstract	This series characterises nine patients with neurohistopathologically proven peripheral nerve neurolymphomatosis. A search of the hospital neuropathology database from 2002 to 2019 identified biopsy proven cases. Clinical data, investigation modalities, treatments, and outcomes were collated. Median age at neuropathy onset was 47 y, the neuropathy commonly as the initial lymphoma disease manifestation. Most (8/9) presented with painful asymmetrical sensory disturbance, with additional cranial nerve involvement in three. Neurophysiology typically demonstrated multiple axonal mononeuropathies. Cerebrospinal fluid protein was often raised (6/8). Magnetic resonance imaging suggested peripheral nerve infiltration in 6/9 and positron emission tomography CT in 4/9. Bone marrow biopsy was abnormal in 6/8. Treatment involved systemic or intrathecal chemotherapy and radiotherapy. Median survival was 23 mo. Neurolymphomatosis is a rare but important cause of neuropathy, particularly in those lacking systemic evidence of lymphoma as correct aggressive treatment can prolong survival. Nerve biopsy is essential to classify lymphoma type and rule out alternatives.
MeSH term(s)	Adult ; Aged ; Biopsy ; Female ; Humans ; Male ; Middle Aged ; Neural Conduction ; Neurolymphomatosis/diagnosis ; Neurolymphomatosis/pathology ; Neurolymphomatosis/therapy ; Peripheral Nervous System Neoplasms/diagnosis ; Peripheral Nervous System Neoplasms/pathology ; Peripheral Nervous System Neoplasms/therapy ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2020-09-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	438353-9
ISSN	1097-4598 ; 0148-639X
ISSN (online)	1097-4598
ISSN	0148-639X
DOI	10.1002/mus.27045
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Zs.A 1449: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Corrigendum to Routine blood monitoring in maintenance Immunoglobulin treatment of inflammatory neuropathy: Is it clinically relevant? [Journal of the Neurological Sciences 408 (2020) 116527].

Keh, R / Khalil, A / Nihoyannopoulos, L / Compton, L / Kapoor, M / Gosal, D / Manji, H / Rossor, A M / Reilly, M M / Lunn, M P / Lavin, T M / Carr, A S

Journal of the neurological sciences

2020 Volume 417, Page(s) 116988

Language	English
Publishing date	2020-07-15
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2020.116988
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Article ; Online: Gene replacement therapy after neuropathy onset provides therapeutic benefit in a model of CMT1X.

Kagiava, A / Richter, J / Tryfonos, C / Karaiskos, C / Heslegrave, A J / Sargiannidou, I / Rossor, A M / Zetterberg, H / Reilly, M M / Christodoulou, C / Kleopa, K A

Human molecular genetics

2019 Volume 28, Issue 21, Page(s) 3528–3542

Abstract: X-linked Charcot-Marie-Tooth disease (CMT1X), one of the commonest forms of inherited demyelinating neuropathy, results from GJB1 gene mutations causing loss of function of the gap junction protein connexin32 (Cx32). The aim of this study was to examine ... ...

Abstract	X-linked Charcot-Marie-Tooth disease (CMT1X), one of the commonest forms of inherited demyelinating neuropathy, results from GJB1 gene mutations causing loss of function of the gap junction protein connexin32 (Cx32). The aim of this study was to examine whether delayed gene replacement therapy after the onset of peripheral neuropathy can provide a therapeutic benefit in the Gjb1-null/Cx32 knockout model of CMT1X. After delivery of the LV-Mpz.GJB1 lentiviral vector by a single lumbar intrathecal injection into 6-month-old Gjb1-null mice, we confirmed expression of Cx32 in lumbar roots and sciatic nerves correctly localized at the paranodal myelin areas. Gjb1-null mice treated with LV-Mpz.GJB1 compared with LV-Mpz.Egfp (mock) vector at the age of 6 months showed improved motor performance at 8 and 10 months. Furthermore, treated mice showed increased sciatic nerve conduction velocities, improvement of myelination and reduced inflammation in lumbar roots and peripheral nerves at 10 months of age, along with enhanced quadriceps muscle innervation. Plasma neurofilament light (NEFL) levels, a clinically relevant biomarker, were also ameliorated in fully treated mice. Intrathecal gene delivery after the onset of peripheral neuropathy offers a significant therapeutic benefit in this disease model, providing a proof of principle for treating patients with CMT1X at different ages.
MeSH term(s)	Animals ; Charcot-Marie-Tooth Disease/genetics ; Charcot-Marie-Tooth Disease/metabolism ; Charcot-Marie-Tooth Disease/pathology ; Charcot-Marie-Tooth Disease/therapy ; Connexins/genetics ; Connexins/metabolism ; Disease Models, Animal ; Female ; Genetic Therapy ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myelin Sheath/metabolism ; Spinal Nerve Roots/metabolism ; Spinal Nerve Roots/pathology ; Gap Junction beta-1 Protein
Chemical Substances	Connexins
Language	English
Publishing date	2019-08-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddz199
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Article ; Online: Thromboembolic risk with IVIg: Incidence and risk factors in patients with inflammatory neuropathy.

Kapoor, Mahima / Spillane, Jennifer / Englezou, Christina / Sarri-Gonzalez, Scherezade / Bell, Robert / Rossor, Alexander / Manji, Hadi / Reilly, Mary M / Lunn, Michael P / Carr, Aisling

Neurology

2019 Volume 94, Issue 6, Page(s) e635–e638

Abstract: Our objective was to evaluate whether IV immunoglobulin (IVIg) increases the risk of thromboembolic events in neurology outpatients with inflammatory neuropathies, as there is conflicting evidence supporting this hypothesis, mainly from non-neurologic ... ...

Abstract	Our objective was to evaluate whether IV immunoglobulin (IVIg) increases the risk of thromboembolic events in neurology outpatients with inflammatory neuropathies, as there is conflicting evidence supporting this hypothesis, mainly from non-neurologic cohorts. We investigated this question over 30 months in our cohort of patients with inflammatory neuropathies receiving regular IVIg and found a greater incidence of arterial and venous thromboembolic events than population-based rates determined by hospital admissions data. Vascular risk factors were more common in the event group but there were no IVIg administration factors that contributed to the risk. This study suggests that IVIg may have a small but contributory role in determining thromboembolic risk in the inflammatory neuropathy cohort and more evidence is required before it is clear whether the current primary prevention guidelines are appropriate in this group of patients.
MeSH term(s)	Anemia, Hemolytic, Autoimmune/therapy ; Ataxia/therapy ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Immunologic Factors/therapeutic use ; Incidence ; Myocardial Infarction/epidemiology ; Ophthalmoplegia/therapy ; Polyneuropathies/therapy ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy ; Pulmonary Embolism/epidemiology ; Retrospective Studies ; Risk Factors ; Small Fiber Neuropathy/therapy ; Stroke/epidemiology ; Superior Vena Cava Syndrome/epidemiology ; Thromboembolism/epidemiology ; Venous Thrombosis/epidemiology
Chemical Substances	Immunoglobulins, Intravenous ; Immunologic Factors
Language	English
Publishing date	2019-12-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000008742
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