- London, London, City of, United Kingdom
Sachit Shah
University College London, Institute of Neurology, Department Member
Anti-HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) myopathy is an immune-mediated necrotising myopathy. Atypical presentations hinder its recognition and its prompt treatment. We present two patients with atypical clinical or... more
Anti-HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) myopathy is an immune-mediated necrotising myopathy. Atypical presentations hinder its recognition and its prompt treatment. We present two patients with atypical clinical or pathological features. A 45-year-old woman had an asymptomatic serum creatine kinase (CK) of ~10 000 IU/L and muscle biopsy showing minimal changes. She then developed slowly progressive proximal weakness, diagnosed as limb-girdle muscular dystrophy but with negative genetics. Twelve years later, now with severe proximal weakness, her MR scan of muscle showed diffuse asymmetrical fatty degeneration, with conspicuous hyperintense STIR signal abnormalities. HMGCR antibodies were positive and she partially improved with immunosuppression. The second patient developed slowly progressive proximal limb weakness with a high serum CK (~4000 IU/L); muscle biopsy showed a lymphocyte infiltrate with angiocentric distribution suggesting vasculitis. Serum HMGCR an...
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In clinical neurology practice, there are few sensitive, specific and responsive serological biomarkers reflecting pathological processes affecting the peripheral nervous system. Instead, we rely on surrogate multimodality biomarkers for... more
In clinical neurology practice, there are few sensitive, specific and responsive serological biomarkers reflecting pathological processes affecting the peripheral nervous system. Instead, we rely on surrogate multimodality biomarkers for diagnosis and management. Correct use and interpretation of the available tests is essential to ensure that appropriate treatments are used and adjusted in a timely fashion. The incorrect application or interpretation of biomarkers can result in misdiagnosis and delays in appropriate treatment. Here, we discuss the uses and limitations of such biomarkers and discuss possible future developments.
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BackgroundLate onset depression (LOD) may precede the diagnosis of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients... more
BackgroundLate onset depression (LOD) may precede the diagnosis of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients with LOD.MethodsIn a cross-sectional design, 36 patients with first onset of a depressive disorder (Diagnostic and Statistical Manual of Mental Disorders IV criteria) diagnosed after the age of 55 (LOD group) and 30 healthy controls (HC) underwent a detailed clinical assessment. In addition, 28/36 patients with LOD and 20/30 HC underwent a head MRI and 29/36 and 25/30, respectively, had dopamine transporter imaging by 123I-ioflupane single-photon emission computed tomography (SPECT) imaging. Image analysis of both scans was performed by a rater blind to the participant group. Results of clinical assessments and imaging results were compared between the two groups.ResultsPatients with LOD (n=36) had significantly worse scores than HC (n=30) on the PD ...
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ObjectiveNeurofilaments are the major scaffolding proteins for the neuronal cytoskeleton, and variants in NEFH have recently been described to cause axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC).MethodsIn this large observational... more
ObjectiveNeurofilaments are the major scaffolding proteins for the neuronal cytoskeleton, and variants in NEFH have recently been described to cause axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC).MethodsIn this large observational study, we present phenotype–genotype correlations on 30 affected and 3 asymptomatic mutation carriers from eight families.ResultsThe majority of patients presented in adulthood with motor-predominant and lower limb-predominant symptoms and the average age of onset was 31.0±15.1 years. A prominent feature was the development of proximal weakness early in the course of the disease. The disease progressed rapidly, unlike other Charcot-Marie-Tooth disease (CMT) subtypes, and half of the patients (53%) needed to use a wheelchair on average 24.1 years after symptom onset. Furthermore, 40% of patients had evidence of early ankle plantarflexion weakness, a feature which is observed in only a handful of CMT subtypes. Neurophysiological studies and MRI of the ...
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Neurofibromatosis type I is a common autosomal dominant inherited disorder of neural crest origin, affecting 1 in 3000 people.1 Plexiform neurofibromas, benign peripheral nerve sheath tumours, are considered pathognomonic of... more
Neurofibromatosis type I is a common autosomal dominant inherited disorder of neural crest origin, affecting 1 in 3000 people.1 Plexiform neurofibromas, benign peripheral nerve sheath tumours, are considered pathognomonic of neurofibromatosis type I. Pelvic involvement is uncommon and is associated with considerable morbidity.1 A 29-year-old man reported 8 years of progressively increasing left hemiscrotal and gluteal swelling. He had noticed numbness over the penis and scrotum, difficulties with ejaculation and experiencing an orgasm, and perineal pain particularly when trying to ejaculate. He could achieve an erection and had preserved sexual drive, and no bladder or bowel symptoms. He took gabapentin and had never used serotonin-selective reuptake inhibitors. There was no family history of neurofibromatosis type I. General examination was normal with no other cutaneous manifestations of neurofibromatosis type I, suggesting a …
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ObjectiveTo summarise the incidental findings detected on brain imaging and blood tests during the first wave of data collection for the Insight 46 study.DesignProspective observational sub-study of a birth cohort.SettingSingle-day... more
ObjectiveTo summarise the incidental findings detected on brain imaging and blood tests during the first wave of data collection for the Insight 46 study.DesignProspective observational sub-study of a birth cohort.SettingSingle-day assessment at a research centre in London, UK.Participants502 individuals were recruited from the MRC National Survey of Health and Development (NSHD), the 1946 British birth cohort, based on pre-specified eligibility criteria; mean age was 70.7 (SD: 0.7) and 49% were female.Outcome measuresData regarding the number and types of incidental findings were summarised as counts and percentages, and 95% confidence intervals were calculated.Results93.8% of participants completed a brain scan (n=471); 4.5% of scanned participants had a pre-defined reportable abnormality on brain MRI (n=21); suspected vascular malformations and suspected intracranial mass lesions were present in 1.9% (n=9) and 1.5% (n=7) respectively; suspected cerebral aneurysms were the single ...
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Mitochondrial disorders are clinically and genetically heterogeneous and are associated with a variety of disease mechanisms. Defects of mitochondrial protein synthesis account for the largest subgroup of disorders manifesting with... more
Mitochondrial disorders are clinically and genetically heterogeneous and are associated with a variety of disease mechanisms. Defects of mitochondrial protein synthesis account for the largest subgroup of disorders manifesting with impaired respiratory chain capacity; yet, only a few have been linked to dysfunction in the protein components of the mitochondrial ribosomes. Here, we report a subject presenting with dyskinetic cerebral palsy and partial agenesis of the corpus callosum, while histochemical and biochemical analyses of skeletal muscle revealed signs of mitochondrial myopathy. Using exome sequencing, we identified a homozygous variant c.215C>T in MRPS25, which encodes for a structural component of the 28S small subunit of the mitochondrial ribosome (mS25). The variant segregated with the disease and substitutes a highly conserved proline residue with leucine (p.P72L) that, based on the high-resolution structure of the 28S ribosome, is predicted to compromise inter-prote...
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To translate the quantitative MRC Centre MRI protocol in Charcot-Marie-Tooth disease type 1A (CMT1A) to a second site; validate its responsiveness in an independent cohort; and test the benefit of participant stratification to increase... more
To translate the quantitative MRC Centre MRI protocol in Charcot-Marie-Tooth disease type 1A (CMT1A) to a second site; validate its responsiveness in an independent cohort; and test the benefit of participant stratification to increase outcome measure responsiveness. Three healthy volunteers were scanned for intersite standardization. For the longitudinal patient study, 11 patients with CMT1A were recruited with 10 patients rescanned at a 12-month interval. Three-point Dixon MRI of leg muscles was performed to generate fat fraction (FF) maps, transferred to a central site for quality control and analysis. Clinical data collected included CMT Neuropathy Score. Test-retest reliability of FF within individual healthy calf muscles at the remote site was excellent: intraclass correlation coefficient 0.79, limits of agreement -0.67 to +0.85 %FF. In patients, mean calf muscle FF was 21.0% and correlated strongly with disease severity and age. Calf muscle FF significantly increased over 12 ...
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Distal myopathies are a diagnostically challenging group of diseases. We wanted to understand the value of MRI in the current clinical setting and explore the potential for optimizing its clinical application. We retrospectively audited... more
Distal myopathies are a diagnostically challenging group of diseases. We wanted to understand the value of MRI in the current clinical setting and explore the potential for optimizing its clinical application. We retrospectively audited the diagnostic workup in a distal myopathy patient cohort, reassessing the diagnosis, whilst documenting the usage of MRI. We established a literature based distal myopathies MRI pattern template and assessed its diagnostic utility in terms of sensitivity, specificity, and potential impact on the diagnostic workup. Fifty-five patients were included; in 38 with a comprehensive set of data the diagnostic work-up was audited. The median time from symptoms onset to diagnosis was 12.1 years. The initial genetic diagnostic rate was 39%; 18% were misdiagnosed as neuropathies and 13% as inclusion body myositis (IBM). Based on 21 publications we established a MRI pattern template. Its overall sensitivity (50%) and specificity (32%) were low. However in some d...
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Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of... more
Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including β-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms. This paper outlines the clinical, cognitive and imaging protocol of…
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The combination of tongue hemianaesthesia, dysgeusia, dysarthria and dysphagia suggests the involvement of multiple cranial nerves. We present a case with sudden onset of these symptoms immediately following wisdom tooth extraction and... more
The combination of tongue hemianaesthesia, dysgeusia, dysarthria and dysphagia suggests the involvement of multiple cranial nerves. We present a case with sudden onset of these symptoms immediately following wisdom tooth extraction and highlight the clinical features that allowed localisation of the lesion to a focal, iatrogenic injury of the lingual nerve and adjacent styloglossus muscle.
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Quantifying muscle water T2 (T2 -water) independently of intramuscular fat content is essential in establishing T2 -water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL-CPMG combines chemical shift... more
Quantifying muscle water T2 (T2 -water) independently of intramuscular fat content is essential in establishing T2 -water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL-CPMG combines chemical shift fat-water separation with T2 relaxometry to obtain such a measure. Here we evaluate the reproducibility and B1 sensitivity of IDEAL-CPMG T2 -water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T2 -water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter-scan interval of 4 weeks using IDEAL-CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T2 -water and the fat signal amplitude muscle regions manually segmen...
Research Interests: Algorithms, Chemistry, Biomedical Engineering, Magnetic Resonance Imaging, Medicine, and 15 moreAdipose tissue, Humans, Female, Feasibility Studies, Male, Clinical Sciences, Middle Aged, Body water, Relaxometry, Image Enhancement, Adult, Repeatability, Reproducibility, Reproducibility of Results, and Sensitivity and Specificity
BackgroundTransthyretin-associated amyloidosis (ATTR) is the commonest cause of hereditary amyloidosis. Age at onset is 50–60 years with average life-expectancy of 7–14 years. Lumbar spinal stenosis also presents in late middle-age;... more
BackgroundTransthyretin-associated amyloidosis (ATTR) is the commonest cause of hereditary amyloidosis. Age at onset is 50–60 years with average life-expectancy of 7–14 years. Lumbar spinal stenosis also presents in late middle-age; related to disc degeneration, spondylolisthesis and age-related degenerative processes, such as WT-TTR amyloid deposition. Mutant-TTR has not been described in this scenario. Recent therapeutic developments in ATTR, with disease modifying potential, make histological evaluation clinically relevant.CaseFamily history prompted screening in an asymptomatic female carrier (heterozygous I84S) at age 42. At age 47 she developed sensory disturbance and pain in the left leg, brought on by exercise and relieved by rest. One year on, exercise tolerance <100 meters and she had sphincter disturbance. Examination revealed decreased pinprick sensation in the L5 dermatome and asymmetry of ankle and knee jerks, pulses were present. A disc bulge at L2/3 with superimpo...
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SummaryContextThe natural history and the optimum management of patients with nonfunctioning pituitary adenomas (NFPAs) are unclear.ObjectiveOur objective was to characterize the natural history of patients with NFPAs managed... more
SummaryContextThe natural history and the optimum management of patients with nonfunctioning pituitary adenomas (NFPAs) are unclear.ObjectiveOur objective was to characterize the natural history of patients with NFPAs managed conservatively.Design and patientsWe conducted a retrospective analysis of patients presenting to a tertiary referral centre between 1986 and 2009. Patients with pituitary adenomas and no clinical or biochemical evidence of hormonal hypersecretion were included. Those presenting with apoplexy or a radiological follow‐up period of less than 1 year were excluded. The pituitary imaging for all patients was re‐examined by two neuroradiologists in consensus.Outcome measuresThe outcome measures were change in tumour size and pituitary hormone function.ResultsSixty‐six patients were managed conservatively for a mean follow‐up period of 4·3 years (range: 1–14·7). Forty‐seven (71%) had a macroadenoma, and nineteen (29%) had a microadenoma. Tumour size decreased or remai...
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Imaging plays an important role in the diagnosis and management of dementia. This review covers the imaging features of the most common dementing illnesses:... more
Imaging plays an important role in the diagnosis and management of dementia. This review covers the imaging features of the most common dementing illnesses: Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD). It describes typical findings on structural neuroimaging and discusses functional and molecular imaging techniques such as FDG PET, amyloid PET, magnetic resonance (MR) perfusion imaging, diffusion tensor imaging (DTI) and functional MR imaging (fMRI).
Research Interests: Neuroimaging, Dementia, Magnetic Resonance Imaging, Diffusion Tensor Imaging, Positron Emission Tomography, and 14 moreMedicine, Diffusion MRI, Humans, Cerebral Cortex, Neuroradiology, Vascular dementia, Female, Male, Differential Diagnosis, Clinical Sciences, Atrophy, Frontotemporal Dementia, Alzheimer Disease, and Dementia With Lewy Bodies
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Research Interests: Nursing, Free Radicals, Acute kidney injury, Stress, Oxidative Stress, and 44 moreCritical, Critical Care, Dendritic Cells, Cell Division, Cell Differentiation, Prospective studies, Humans, Age, Reactive Oxygen Species, Female, Animals, System, Male, Antigen Presentation, Dendritic cell, TNF, Page, Clinical Sciences, Oxidative stress and free radical biology and medicine, Cattle, Intensive Care Unit, IL, T lymphocytes, Aged, Middle Aged, Lipopolysaccharides, Adult, Monocytes, PBS, Biological markers, HBSS, Intensive Care Units, Bovine Serum Albumin, Alpha, Advanced Oxidation Protein Products, PBMC, Oxidation-Reduction, Critical Illness, Blood Proteins, Tyrosine, Biochemistry and cell biology, Interleukin, Serum albumin, and Severity of Illness Index
There have been substantial advances in pituitary imaging in the last half-century. In particular, magnetic resonance imaging is now established as the imaging modality of choice, providing high quality images of the... more
There have been substantial advances in pituitary imaging in the last half-century. In particular, magnetic resonance imaging is now established as the imaging modality of choice, providing high quality images of the hypothalamic-pituitary axis and adjacent structures. More recent technological advances, such as the emergence of 3 Tesla MRI, are already being widely incorporated into imaging practice. However, other advanced techniques, including a variety of potential imaging biomarkers, still require further research to evaluate their potential and define their precise role. The recent development of intraoperative MRI appears promising and may have the potential to improve the outcome of pituitary surgery. Modern high quality imaging inevitably leads to the discovery of incidental lesions, including those within the pituitary gland, although it also plays a central role in their subsequent evaluation and management.
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Background Multifocal lymphangiomatosis is a rare systemic disorder affecting children. Due to its rarity and wide spectrum of clinical, histological and imaging features, establishing the diagnosis of multifocal lymphangiomatosis can be... more
Background Multifocal lymphangiomatosis is a rare systemic disorder affecting children. Due to its rarity and wide spectrum of clinical, histological and imaging features, establishing the diagnosis of multifocal lymphangiomatosis can be challenging. Objectives The purpose of this study was to describe a new imaging sign in this disorder: paraspinal soft tissue and signal abnormality at MRI. Materials and methods We retrospectively reviewed the imaging, clinical and histopathological findings in a cohort of eight children with thoracic involvement from this condition. Results Evidence of paraspinal chest disease was identified at MRI and CT in all eight of these children. The changes comprise heterogeneous intermediate-to-high signal parallel to the thoracic vertebrae on T2-weighted sequences at MRI, with abnormal paraspinal soft tissue at CT and plain radiography. Conclusion Multifocal lymphangiomatosis is a rare disorder with a broad range of clinicopathological and imaging features. MRI allows complete evaluation of disease extent without the use of ionising radiation and has allowed us to describe a previously unreported imaging sign in this disorder, namely, heterogeneous hyperintense signal in abnormal paraspinal tissue on T2-weighted images.