ORCID Profile
0000-0001-5498-3426
Current Organisations
UCL Institute of Neurology, University College London
,
Monash University
,
The Alfred Hospital
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Publisher: BMJ
Date: 14-02-2019
DOI: 10.1136/JNNP-2019-ABN.131
Abstract: Hereditary Transthyretin (ATTR) amyloidosis is a genetic disorder where insoluble amyloid fibrils deposit in heart, nerves and various musculoskeletal tissues. Early recognition of TTR-FAP is important as new genetic therapies become available. We present one confirmed and one clinical case of ATTR deposition in ligamentum flavum causing lumbar canal stenosis. The first case is a 44-year-old female with TTR 184S heterozygous mutation who developed urinary urgency and bilateral leg pain exacerbated by walking. Neurological examination was normal. MRI lumbar spine showed a disc bulge in combination with ligamentum flavum thickening at L2/3 causing stenosis of the vertebral canal. She had a laminectomy of the L2/3 level. Histopathological analysis of the surgical tissue was positive on Congo red staining for amyloid and immunohistochemically identified as TTR type. The second case is a 68-year-old man with TTR V122I heterozygous mutation. He presented with paraesthesia from the knees to dorsum of the feet. On examination, power was normal and he had a length dependent neuropathy. A CT myelogram demonstrated spondylosis at L4/5 and L3/4 from disc bulge and marked flaval hypertrophy causing canal stenosis. He was placed on the waitlist for L4-5 decompression but unfortunately died prior to surgery. Identifying ATTR in surgical specimens may diagnose hereditary amyloidosis in otherwise asymptomatic patients and in the future, provide early access to effective therapies.
Publisher: Wiley
Date: 25-07-2022
DOI: 10.1111/ENE.15496
Abstract: 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. 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. 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. pNfL concentrations may be a sensitive, clinically useful biomarker in assessing subclinical disease activity.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Wiley
Date: 14-10-2019
DOI: 10.1111/JNS.12350
Abstract: Hereditary transthyretin amyloidosis (ATTRm) causes a disabling peripheral neuropathy as part of a multisystem disorder. The recent development of highly effective gene silencing therapies has highlighted the need for effective biomarkers of disease activity to guide the decision of when to start and stop treatment. In this study, we measured plasma neurofilament light chain (pNfL) concentration in 73 patients with ATTR and found that pNfL was significantly raised in ATTRm patients with peripheral neuropathy compared to healthy controls. Furthermore, pNFL correlated with disease severity as defined by established clinical outcome measures in patients for whom this information was available. These findings suggest a potential role of pNfL in monitoring disease activity and progression in ATTRm patients.
Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJNO-2020-000101
Abstract: COVID-19 is a significant global health burden. The pulmonary morbidity and mortality of COVID-19 is well described, however, there is mounting evidence of neurological manifestations of SARS-CoV-2, which may be of prognostic significance. This paper summarises the available evidence in order to provide clinicians with a concise summary of the peripheral and central neurological manifestations of COVID-19, discusses specific issues regarding the management of chronic neurological disease in the context of the pandemic, and provides a summary of the thrombotic implications of the disease for the neurologist.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2021
Publisher: Wiley
Date: 26-03-2018
DOI: 10.1111/JNS.12260
Publisher: Elsevier BV
Date: 04-2018
Publisher: Wiley
Date: 20-10-2021
DOI: 10.1111/JNS.12470
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 in iduals 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 ( % 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.
Publisher: BMJ
Date: 30-12-2019
DOI: 10.1136/PRACTNEUROL-2018-002098
Abstract: Systemic amyloidosis can be hereditary or acquired. The autosomal dominant hereditary transthyretin amyloidosis and the acquired light-chain amyloidosis, the result of a plasma cell dyscrasia, are multisystem disorders with cardiovascular, autonomic and peripheral nerve involvement. There are numerous investigational modalities available to diagnose systemic amyloidosis and to assess the extent of organ involvement, but it is frequently misdiagnosed due to its heterogeneous clinical presentations and misleading investigation findings. An accurate and timely diagnosis of amyloid neuropathy can greatly impact on the outcomes for patients, especially as there will soon be new gene-silencing treatments for hereditary transthyretin amyloidosis.
Publisher: BMJ
Date: 30-03-2002
Abstract: To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy. Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment. Patients with any stage of HIV infection who had not received antiretroviral therapy. Changes in disease progression or death (clinical outcomes) CD4 count and plasma viral load (surrogate markers). Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001. 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality. Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.74
Abstract: Identifying patients who need long-term immunoglobulin (IVIg) treatment in patient with inflammatory neuropathies is essential as recent treatment trials show a remission rate of up to 40%. Compare retrospective data on clinical, investigational and treatment factors in patients who have ceased IVIg with patients who have failed a cessation trial. 15 patients who successfully suspended IVIg infusions were compared with 15 in whom decreasing or stopping IVIg was unsuccessful. 30 patients (12 with CIDP and 3 with MMN in both groups) were diagnosed 39.5 months from onset of symptoms in the successful group vs. 40.7 months in the unsuccessful group (p=0.953). There was a significant difference in the summed upper limb sensory litudes on electrophysiology prior to starting IVIg between the patients with CIDP (17.4 mV vs. 9.8mV p=0.007). There was no difference in the average doses between the groups. A successful cessation trial was attempted at a mean of 60.5 months post starting treatment, compared with 60 months in the unsuccessful patients. There is a need for objective biomarker to measure disease activity because other than one neurophysiology marker, other factors did not help predict a successful cessation trial of IVIg.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-12-2020
DOI: 10.1212/WNL.0000000000008742
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.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Frontiers Media SA
Date: 27-06-2019
Publisher: Informa UK Limited
Date: 03-09-2022
DOI: 10.1080/00207454.2020.1815733
Abstract: Intravenous immunoglobulin (IVIg) has short and long-term efficacy in both chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). There is potential for under and over-treatment if trial regimens are strictly adhered to in clinical practice where titrating dose to clinical response is recommended. We report the response to high-dose IVIg (>2 g/kg/6 weeks) in a subgroup of patients with definite CIDP or MMNCB who were unresponsive to 'usual' dosing. IVIg frequency and dosing was determined for each in idual by subjective and objective outcome measures for impairment, grip strength, and activity and participation. Six patients (three with chronic inflammatory demyelinating polyneuropathy (CIDP), three with MMN) were included. Two patients (one CIDP and one MMNCB) returned to full-time work on fractionated IVIg doses of 5 g/kg/month and 9 g/kg/month. Patient three (CIDP) failed numerous other immunosuppressants but responded to short-term fractionated 4 g/kg/month of IVIg. Patient four has severe, refractory, childhood-onset CIDP, remains stable but dependent currently on 6.9 g/kg/month of IVIg. Patients five and six, both with MMNCB, required short term 4.5-5 g/kg/month to recover significant bilateral hand strength. No IVIg-related adverse events occurred in any in idual. These six cases demonstrate the safety and effectiveness of a treatment approach that includes in idualised but evidence-based clinical assessment and, when necessary, high-doses of IVIg to restore patients' strength and ability to participate in activities of daily activities. Careful patient selection is important.
Publisher: BMJ
Date: 10-06-2022
Abstract: Arterial and venous thromboembolic events (TEEs) have been associated with intravenous Ig use, but the risk has been poorly quantified. We aimed to calculate the risk of TEEs associated with exposure to intravenous Ig. We included participants from UK Biobank recruited over 3 years, data extracted September 2020. The study endpoints were incidence of myocardial infarction, other acute ischaemic heart disease, stroke, pulmonary embolism and other venous embolism and thrombosis. Predictors included known TEE risk factors: age, sex, hypertension, smoking status, type 2 diabetes mellitus, hypercholesterolaemia, cancer and past history of TEE. Intravenous Ig and six other predictors were added in the sensitivity analysis. Information from participants was collected prospectively, while data from linked resources, including death, cancer, hospital admissions and primary care records were collected retrospectively and prospectively. 14 794 of 502 492 in iduals had an incident TEE during the study period. The rate of incident events was threefold higher in those with prior history of TEE (8 .7%) than those without previous history of TEE (3.0%). In the prior TEE category, intravenous Ig exposure was independently associated with increased risk of incident TEE (OR=3.69 (95% CI 1.15 to 11.92), p=0.03) on multivariate analysis. The number needed to harm by exposure to intravenous Ig in those with a history of TEE was 5.8 (95% CI 2.3 to 88.3). Intravenous Ig exposure did not increase risk of TEE in those with no previous history of TEE. Intravenous Ig is associated with increased risk of further TEE in in iduals with prior history of an event with one further TEE for every six people exposed. In practice, this will influence how clinicians consent for and manage overall TEE risk on intravenous Ig exposure.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JNS.2019.116527
Abstract: Pre-treatment screening for IgA deficiency and close monitoring of full blood count(FBC) and renal function is recommended with intravenous immunoglobulin(IVIg) therapy in neurological diseases. To examine the frequency of biochemically defined and clinically significant episodes of treatment associated haemolysis, neutropenia, thrombocytopenia and acute kidney injury(AKI) in a cohort of patients on maintenance Immunoglobulin(Ig) therapy for inflammatory neuropathy. A retrospective review of routine blood monitoring in patients from two UK specialist peripheral nerve centres. Accepted definitions for clinically and biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used. 1919 infusion episodes in 90 patients were analysed. Age(mean(S.D)) = 58.09(14.4)years, 63% male, 72% CIDP(28% MMN), 97% IVIg(3% SCIg). Dose = 1.57(0.79)g/kg/month or 97.1(37.3)g/infusion, frequency:3.9(1.4) weeks. Relative IgA deficiency was noted in 2 in iduals (prevalence:2.2%, 95%C.I.:0-5.2) who received a combined total of 38 infusions(3800 g IVIg) without adverse event. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to treatment. An asymptomatic drop>10 g/L haemoglobin(Hb) occurred in 3.5%(95%CI:2.7-4.3) of treatment episodes in 38 in iduals, mean reduction:17.7(7.4)g/L lowest Hb:86 g/L. Lower pre-treatment haemoglobin correlated with risk of recurrent Ig-related drop(p:0.007). Two patients with chronic renal failure(stage 1 and 3) received 28(IV) and 104(SC) infusions respectively(6416 g) without impact on estimated glomerular filtration rate(eGFR). No clinically significant Ig-related episodes of haemolysis or AKI were identified in this representative cohort. This suggests that routine monitoring is not essential in long-term Ig use but should be considered when clinically indicated.
Publisher: Wiley
Date: 17-12-2020
DOI: 10.1111/ENE.14649
Abstract: Pathogenic variants in PLEKHG5 have been reported to date to be causative in three unrelated families with autosomal recessive intermediate Charcot‐Marie‐Tooth disease (CMT) and in one consanguineous family with spinal muscular atrophy (SMA). PLEKHG5 is known to be expressed in the human peripheral nervous system, and previous studies have shown its function in axon terminal autophagy of synaptic vesicles, lending support to its underlying pathogenetic mechanism. Despite this, there is limited knowledge of the clinical and genetic spectrum of disease. We leverage the diagnostic utility of exome and genome sequencing and describe novel biallelic variants in PLEKHG5 in 13 in iduals from nine unrelated families originating from four different countries. We compare our phenotypic and genotypic findings with a comprehensive review of cases previously described in the literature. We found that patients presented with variable disease severity at different ages of onset (8–25 years). In our cases, weakness usually started proximally, progressing distally, and can be associated with intermediate slow conduction velocities and minor clinical sensory involvement. We report three novel nonsense and four novel missense pathogenic variants associated with these PLEKHG5 ‐associated neuropathies, which are phenotypically spinal muscular atrophy (SMA) or intermediate Charcot‐Marie‐Tooth disease. PLEKHG5 ‐associated neuropathies should be considered as an important differential in non‐5q SMAs even in the presence of mild sensory impairment and a candidate causative gene for a wide range of hereditary neuropathies. We present this series of cases to further the understanding of the phenotypic and molecular spectrum of PLEKHG5 ‐associated diseases.
Publisher: BMJ
Date: 13-09-2018
DOI: 10.1136/JNNP-2018-ABN.121
Abstract: ABN immunoglobulin (Ig) guidelines advise routine FBC and U and E monitoring with every treatment episode and screening for IgA deficiency. We audited compliance in inflammatory neuropathy patients on longterm treatment in two UK Neurology departments. We looked for evidence of clinically relevant haematological or AKI Ig-related events. Data was collected from Nov 2015 to Nov 2017. Accepted definitions for clinically and/or biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used. 1919 treatment episodes in 90 patients were analysed. Mean age (SD)=57.6 (14.4)years, 69.1% male, 74% CIDP (26% MMN), 94% IVIg (6% SCIg). Mean dose=1.57 (0.74) g/kg/month or 97.1 (37.3) g/infusion. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to Ig treatment. An asymptomatic drop of g/L Hb occurred in 68/1919 episodes in 38 in iduals (3.5%) mean reduction 17.7 g/L, lowest Hb 99 g/L. Two patients with CRF (stage 3) received 28 (IV) and 104 (SC) infusions respectively without impact on eGFR. Two in iduals with relative IgA deficiency (0.38 g/L, 0.4 g/L) received 16 infusions over 1.5 years without complications. No clinically significant Ig-related events were identified in this representative cohort. We suggest annual screening or clinically indicated testing as safe and more appropriate in longterm IVIg use.
Publisher: BMJ
Date: 14-02-2019
Abstract: Intraneural perineurioma is a rare, benign neoplasm of peripheral nerve. The histopathological features are well defined. We describe 5 cases of histologically confirmed perineuriomas and 14 cases diagnosed on clinical and radiological characteristics to highlight the features of this rare entity. We identified cases from the imaging and histopathology database and conducted a retrospective case note review. The subjects include 7 men and 12 women, with mean (standard deviation) age of 17.64 (13) years at onset of symptoms. 14 of the 15 lower limb cases were located in the sciatic nerve or its isions. 1 each was identified in ulnar, median and radial nerves and 1 case was in a facial nerve. The MRI features were homogenous between the groups. The nerves biopsied included 1 tibial, 1 ulnar, 1 radial, 1 facial and 1 sciatic all showing classic pathology findings. 2 patients, interestingly, had coincidental intracranial meningioma, given the recent discovery of a potential shared pathogenesis (mutations in TRAF7) with intracranial meningiomas. 2 patients had ‘skip lesions’ within the same nerve and 3 patients had foraminal and extraforaminal involvement of lumbosacral nerve roots. Our unit now favours the clinicoradiological features for diagnosing perineuriomas rather than performing a biopsy on all patients. Also, the potential shared pathogenesis with meningiomas raises the clinical issue of screening in patients with perineuriomas but more clinical evidence is required.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: No location found
No related grants have been discovered for Mahima Kapoor.