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Background: While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods: A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72. A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results: Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72-positive ALS patients. Conclusions: Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype.
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INTRODUCTION: Pseudobulbar affect (PBA) is a distressing symptom of a multitude of neurological conditions affecting patients with a rage of neuroinflammatory, neurovascular and neurodegenerative conditions. It manifests in disproportionate emotional responses to minimal or no contextual stimulus. It has considerable quality of life implications and treatment can be challenging. METHODS: A prospective multimodal neuroimaging study was conducted to explore the neuroanatomical underpinnings of PBA in patients with primary lateral sclerosis (PLS). All participants underwent whole genome sequencing and screening for C9orf72 hexanucleotide repeat expansions, a comprehensive neurological assessment, neuropsychological screening (ECAS, HADS, FrSBe) and PBA was evaluated by the emotional lability questionnaire. Structural, diffusivity and functional MRI data were systematically evaluated in whole-brain (WB) data-driven and region of interest (ROI) hypothesis-driven analyses. In ROI analyses, functional and structural corticobulbar connectivity and cerebello-medullary connectivity alterations were evaluated separately. RESULTS: Our data-driven whole-brain analyses revealed associations between PBA and white matter degeneration in descending corticobulbar as well as in commissural tracts. In our hypothesis-driven analyses, PBA was associated with increased right corticobulbar tract RD (p = 0.006) and decreased FA (p = 0.026). The left-hemispheric corticobulbar tract, as well as functional connectivity, showed similar tendencies. While uncorrected p-maps revealed both voxelwise and ROI trends for associations between PBA and cerebellar measures, these did not reach significance to unequivocally support the "cerebellar hypothesis". CONCLUSIONS: Our data confirm associations between cortex-brainstem disconnection and the clinical severity of PBA. While our findings may be disease-specific, they are consistent with the classical cortico-medullary model of pseudobulbar affect.
Subject(s)
Cerebellum , Cerebral Cortex , Crying , Laughter , Models, Neurological , Motor Neuron Disease , Pyramidal Tracts , Radiology , Aged , Female , Humans , Male , Middle Aged , Amyotrophic Lateral Sclerosis/complications , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/pathology , Amyotrophic Lateral Sclerosis/physiopathology , Cerebellum/diagnostic imaging , Cerebellum/pathology , Cerebellum/physiopathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Frontal Lobe/physiopathology , Magnetic Resonance Imaging , Medulla Oblongata/diagnostic imaging , Medulla Oblongata/pathology , Medulla Oblongata/physiopathology , Motor Cortex/diagnostic imaging , Motor Cortex/pathology , Motor Cortex/physiopathology , Motor Neuron Disease/complications , Motor Neuron Disease/diagnostic imaging , Motor Neuron Disease/pathology , Motor Neuron Disease/physiopathology , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/pathology , Pyramidal Tracts/physiopathology , Quality of Life , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology , Temporal Lobe/physiopathologyABSTRACT
BACKGROUND: Bulbar dysfunction is a cardinal feature of ALS with important quality of life and management implications. The objective of this study is the longitudinal evaluation of a large panel imaging metrics pertaining to bulbar dysfunction, encompassing cortical measures, structural and functional cortico-medullary connectivity indices and brainstem metrics. METHODS: A standardised, multimodal imaging protocol was implemented with clinical and genetic profiling to systematically appraise the biomarker potential of specific metrics. A total of 198 patients with ALS and 108 healthy controls were included. RESULTS: Longitudinal analyses revealed progressive structural and functional disconnection between the motor cortex and the brainstem over time. Cortical thickness reduction was an early feature on cross-sectional analyses with limited further progression on longitudinal follow-up. Receiver operating characteristic analyses of the panel of MR metrics confirmed the discriminatory potential of bulbar imaging measures between patients and controls and area-under-the-curve values increased significantly on longitudinal follow-up. C9orf72 carriers exhibited lower brainstem volumes, lower cortico-medullary structural connectivity and faster cortical thinning. Sporadic patients without bulbar symptoms, already exhibit significant brainstem and cortico-medullary connectivity alterations. DISCUSSION: Our results indicate that ALS is associated with multi-level integrity change from cortex to brainstem. The demonstration of significant corticobulbar alterations in patients without bulbar symptoms confirms considerable presymptomatic disease burden in sporadic ALS. The systematic assessment of radiological measures in a single-centre academic study helps to appraise the diagnostic and monitoring utility of specific measures for future clinical and clinical trial applications.
Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Amyotrophic Lateral Sclerosis/complications , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/genetics , Cross-Sectional Studies , Quality of Life , Magnetic Resonance Imaging/methods , Brain Stem/diagnostic imaging , Biomarkers , HeterozygoteABSTRACT
BACKGROUND AND PURPOSE: Primary lateral sclerosis (PLS) is a progressive upper motor neuron disorder associated with considerable clinical disability. Symptoms are typically exclusively linked to primary motor cortex degeneration and the contribution of pre-motor, supplementary motor, cortico-medullary and inter-hemispheric connectivity alterations are less well characterized. METHODS: In a single-centre, prospective, longitudinal neuroimaging study 41 patients with PLS were investigated. Patients underwent standardized neuroimaging, genetic profiling with whole exome sequencing, and comprehensive clinical assessments including upper motor neuron scores, tapping rates, mirror movements, spasticity assessment, cognitive screening and evaluation for pseudobulbar affect. Longitudinal neuroimaging data from 108 healthy controls were used for image interpretation. A standardized imaging protocol was implemented including 3D T1-weighted structural, diffusion tensor imaging and resting-state functional magnetic resonance imaging. Following somatotopic segmentation, cortical thickness analyses, probabilistic tractography, blood oxygenation level dependent signal analyses and brainstem volumetry were conducted to evaluate cortical, brainstem, cortico-medullary and inter-hemispheric connectivity alterations both cross-sectionally and longitudinally. RESULTS: Our data confirm progressive primary motor cortex degeneration, considerable supplementary motor and pre-motor area involvement, progressive brainstem atrophy, cortico-medullary and inter-hemispheric disconnection, and close associations between clinical upper motor neuron scores and somatotopic connectivity indices in PLS. DISCUSSION: Primary lateral sclerosis is associated with relentlessly progressive motor connectome degeneration. Clinical disability in PLS is likely to stem from a combination of intra- and inter-hemispheric connectivity decline and primary, pre- and supplementary motor cortex degeneration. Simple 'bedside' clinical tools, such as tapping rates, are excellent proxies of the integrity of the relevant fibres of the contralateral corticospinal tract.
Subject(s)
Amyotrophic Lateral Sclerosis , Connectome , Motor Neuron Disease , Humans , Amyotrophic Lateral Sclerosis/genetics , Diffusion Tensor Imaging , Prospective Studies , Magnetic Resonance Imaging/methods , Motor Neuron Disease/diagnostic imagingABSTRACT
While primary lateral sclerosis (PLS) has traditionally been regarded as a pure upper motor neuron disorder, recent clinical, neuroimaging and postmortem studies have confirmed significant extra-motor involvement. Sporadic reports have indicated that in addition to the motor cortex and corticospinal tracts, the cerebellum may also be affected in PLS. Cerebellar manifestations are difficult to ascertain in PLS as the clinical picture is dominated by widespread upper motor neuron signs. The likely contribution of cerebellar dysfunction to gait disturbance, falls, pseudobulbar affect and dysarthria may be overlooked in the context of progressive spasticity. The objective of this study is the comprehensive characterization of cerebellar gray and white matter degeneration in PLS using multiparametric quantitative neuroimaging methods to systematically evaluate each cerebellar lobule and peduncle. Forty-two patients with PLS and 117 demographically-matched healthy controls were enrolled in a prospective MRI study. Complementary volumetric and voxelwise analyses revealed focal cerebellar alterations instead of global cerebellar atrophy. Bilateral gray matter volume reductions were observed in lobules III, IV and VIIb. Significant diffusivity alterations within the superior cerebellar peduncle indicate disruption of the main cerebellar outflow tracts. These findings suggest that the considerable intra-cerebellar disease-burden is coupled with concomitant cerebro-cerebellar connectivity disruptions. While cerebellar dysfunction is challenging to demonstrate clinically, cerebellar pathology is likely to be a significant contributor to disability in PLS.
Subject(s)
Amyotrophic Lateral Sclerosis , Cerebellar Diseases , Motor Neuron Disease , Humans , Amyotrophic Lateral Sclerosis/diagnosis , Prospective Studies , Motor Neuron Disease/pathology , Neuroimaging , Magnetic Resonance ImagingABSTRACT
AIM: To compare the associated discomfort and safety between transcutaneous (Tskin) and transconjunctival (Tconj) approaches of local anaesthetic (LA) administration in lower eyelid surgery. METHODS: A prospective randomised controlled trial comparing Tskin and Tconj LA in patients undergoing bilateral lower eyelid surgeries for horizontal laxity. Patients were randomised to receive LA via Tskin to one side and Tconj to the fellow side. LA injection was administered in a slow fashion accompanied by distraction (tapping of patient's forehead). Self-reported discomfort from the injections was rated using a 0-10 numerical rating scale. A single blinded assessor graded photographs for eyelid bruising (0 = absent, 1 = mild, 2 = moderate, 3 = severe). RESULTS: A total of 30 patients (mean age ± SD, 75.9 ± 6.7 years) were enrolled. The overall pain score (mean ± SD) was statistically lower for the Tconj than the Tskin group (3.90 ± 2.28 versus 5.33 ± 2.23, p = 0.017). More patients in the Tconj group reported substantially less pain (score of ≤3) in comparison to the Tskin group (56.7% versus 23.3%, p = 0.017). In individual patients, the Tconj pain score was found to be significantly lower than the Tskin side (p = 0.008). Bruising scores were higher in the Tskin group, but this was not statistically significant (p = 0.13). No other adverse effects were found. CONCLUSION: Tconj delivery of LA in lower eyelids with horizontal laxity is safe and associated with less discomfort and bruising than the conventional Tskin route. TRIAL REGISTRATION NUMBER: NCT04102878.
Subject(s)
Anesthesia, Local , Anesthetics, Local , Eyelids/surgery , Humans , Pain , Prospective StudiesABSTRACT
OBJECTIVES: To determine whether cataract surgery is associated with an increased risk of subsequent lower eyelid entropion and evaluate potential associated factors. METHODS: This retrospective cohort study included consecutive patients undergoing first eye cataract surgery over a 10-year period at a single institution (n = 14,574). The fellow phakic eye served as control. Patient records were evaluated up until either the time of second eye cataract surgery or any other intraocular or adnexal surgery. The primary outcome was the rate of entropion repair in both the pseudophakic (exposed) group and the phakic control group. Groups were compared using relative risk and Kaplan-Meier analysis. Multivariate logistic regression was used to compare pre-specified characteristics of those patients that underwent entropion repair in their pseudophakic eye with those that did not. RESULTS: A fourfold higher relative risk of undergoing entropion repair was observed in eyes that had undergone cataract surgery compared with the fellow unoperated eye (95% confidence interval 1.6-9.8; P < 0.001) with an increased risk at all timepoints between 1 and 12 years according to Kaplan-Meier analysis (P = 0.001). Median time to entropion repair after cataract surgery was 58 months (range 3-124). Documented intraoperative patient factors such as patient or eye movement, eyelid squeezing, pain or anxiety were an independent risk factor for subsequent entropion (P < 0.0001). CONCLUSIONS: Cataract surgery is associated with an increased risk of subsequent lower eyelid entropion. Surgeons should be aware of this risk in the pre- and post-operative assessment of patients undergoing cataract surgery.
Subject(s)
Cataract Extraction , Cataract , Entropion , Cataract Extraction/adverse effects , Entropion/etiology , Entropion/surgery , Eyelids/surgery , Humans , Retrospective StudiesABSTRACT
Frontotemporal involvement has been extensively investigated in amyotrophic lateral sclerosis (ALS) but remains relatively poorly characterized in other motor neuron disease (MND) phenotypes such as primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), spinal muscular atrophy (SMA), spinal bulbar muscular atrophy (SBMA), post poliomyelitis syndrome (PPS), and hereditary spastic paraplegia (HSP). This review focuses on insights from structural, metabolic, and functional neuroimaging studies that have advanced our understanding of extra-motor disease burden in these phenotypes. The imaging literature is limited in the majority of these conditions and frontotemporal involvement has been primarily evaluated by neuropsychology and post mortem studies. Existing imaging studies reveal that frontotemporal degeneration can be readily detected in ALS and PLS, varying degree of frontotemporal pathology may be captured in PMA, SBMA, and HSP, SMA exhibits cerebral involvement without regional predilection, and there is limited evidence for cerebral changes in PPS. Our review confirms the heterogeneity extra-motor pathology across the spectrum of MNDs and highlights the role of neuroimaging in characterizing anatomical patterns of disease burden in vivo. Despite the contribution of neuroimaging to MND research, sample size limitations, inclusion bias, attrition rates in longitudinal studies, and methodological constraints need to be carefully considered. Frontotemporal involvement is a quintessential clinical facet of MND which has important implications for screening practices, individualized management strategies, participation in clinical trials, caregiver burden, and resource allocation. The academic relevance of imaging frontotemporal pathology in MND spans from the identification of genetic variants, through the ascertainment of presymptomatic changes to the design of future epidemiology studies.
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While C9orf72-specific imaging signatures have been proposed by both ALS and FTD research groups and considerable presymptomatic alterations have also been confirmed in young mutation carriers, considerable inconsistencies exist in the literature. Accordingly, a systematic review of C9orf72-imaging studies has been performed to identify consensus findings, stereotyped shortcomings, and unique contributions to outline future directions. A formal literature review was conducted according to the STROBE guidelines. All identified papers were individually reviewed for sample size, choice of controls, study design, imaging modalities, statistical models, clinical profiling, and identified genotype-associated pathological patterns. A total of 74 imaging papers were systematically reviewed. ALS patients with GGGGCC repeat expansions exhibit relatively limited motor cortex involvement and widespread extra-motor pathology. C9orf72 positive FTD patients often show preferential posterior involvement. Reports of thalamic involvement are relatively consistent across the various phenotypes. Asymptomatic hexanucleotide repeat carriers often exhibit structural and functional changes decades prior to symptom onset. Common shortcomings included sample size limitations, lack of disease-controls, limited clinical profiling, lack of genetic testing in healthy controls, and absence of post mortem validation. There is a striking paucity of longitudinal studies and existing presymptomatic studies have not evaluated the predictive value of radiological changes with regard to age of onset and phenoconversion. With the advent of antisense oligonucleotide therapies, the meticulous characterisation of C9orf72-associated changes has gained practical relevance. Neuroimaging offers non-invasive biomarkers for future clinical trials, presymptomatic ascertainment, diagnostic and prognostic applications.
Subject(s)
Amyotrophic Lateral Sclerosis , Frontotemporal Dementia , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/genetics , C9orf72 Protein/genetics , DNA Repeat Expansion/genetics , Frontotemporal Dementia/genetics , Humans , Magnetic Resonance Imaging , Proteins/geneticsABSTRACT
Purpose: To evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes. Design: Double-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365). Participants: Sixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo. Methods: Macular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit. Main Outcome Measures: Change in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months. Results: A mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial. Conclusions: Macular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.
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Presymptomatic studies in ALS have consistently captured considerable disease burden long before symptom manifestation and contributed important academic insights. With the emergence of genotype-specific therapies, however, there is a pressing need to address practical objectives such as the estimation of age of symptom onset, phenotypic prediction, informing the optimal timing of pharmacological intervention, and identifying a core panel of biomarkers which may detect response to therapy. Existing presymptomatic studies in ALS have adopted striking different study designs, relied on a variety of control groups, used divergent imaging and electrophysiology methods, and focused on different genotypes and demographic groups. We have performed a systematic review of existing presymptomatic studies in ALS to identify common themes, stereotyped shortcomings, and key learning points for future studies. Existing presymptomatic studies in ALS often suffer from sample size limitations, lack of disease controls and rarely follow their cohort until symptom manifestation. As the characterisation of presymptomatic processes in ALS serves a multitude of academic and clinical purposes, the careful review of existing studies offers important lessons for future initiatives.
Subject(s)
Amyotrophic Lateral Sclerosis , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/genetics , Humans , Sample SizeABSTRACT
A standardised imaging protocol was implemented to evaluate disease burden in specific thalamic and amygdalar nuclei in 133 carefully phenotyped and genotyped motor neuron disease patients. "Switchboard malfunction in motor neuron diseases: selective pathology of thalamic nuclei in amyotrophic lateral sclerosis and primary lateral sclerosis" [1] "Amygdala pathology in amyotrophic lateral sclerosis and primary lateral sclerosis" [2] Raw volumetric data, group comparisons, effect sizes and percentage change are presented. Both ALS and PLS patients exhibited focal thalamus atrophy in ventral lateral and ventral anterior regions revealing extrapyramidal motor degeneration. Reduced accessory basal nucleus and cortical nucleus volumes were noted in the amygdala of C9orf72 negative ALS patients compared to healthy controls. ALS patients carrying the GGGGCC hexanucleotide repeats in C9orf72 exhibited preferential pathology in the mediodorsal-paratenial-reuniens thalamic nuclei and in the lateral nucleus and cortico-amygdaloid transition area of the amygdala. Considerable thalamic atrophy was observed in the sensory nuclei and lateral geniculate region of PLS patients. Our data demonstrate genotype-specific patterns of thalamus and amygdala involvement in ALS and a distinct disease-burden pattern in PLS. The dataset may be utilised for validation purposes, meta-analyses and the interpretation of thalamic and amygdalar profiles from other ALS genotypes.
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Primary lateral sclerosis (PLS) is an adult-onset upper motor neuron disease manifesting in progressive spasticity and gradually resulting in considerably motor disability. In the absence of early disease-specific diagnostic indicators, the majority of patients with PLS face a circuitous diagnostic journey. Until the recent publication of consensus diagnostic criteria, 4-year symptom duration was required to establish the diagnosis. The new diagnostic criteria introduced the category of 'probable PLS' for patients with a symptom duration of 2-4 years. "Evolving diagnostic criteria in primary lateral sclerosis: The clinical and radiological basis of "probable PLS" [1]. This dataset provides radiological metrics in a cohort of 'probable PLS' patients, 'definite PLS' patients and age-matched healthy controls. Region-of-interest radiological data include diffusivity metrics in the corticospinal tracts and corpus callosum as well as mean cortical thickness values in the pre- and para-central gyri in each hemisphere. Our data indicate considerable grey matter and relatively limited white matter involvement in 'probable PLS' which supports the rationale for this diagnostic category as a clinically useful entity. The introduction of this diagnostic category will likely facilitate the timely recruitment of PLS patients into research studies and pharmacological trials before widespread neurodegenerative change ensues.
Subject(s)
Amyotrophic Lateral Sclerosis , Frontotemporal Dementia , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/genetics , C9orf72 Protein/genetics , Child , DNA Repeat Expansion , Developmental Disabilities , Frontotemporal Dementia/diagnostic imaging , Frontotemporal Dementia/genetics , Humans , NeuroimagingABSTRACT
INTRODUCTION: Primary lateral sclerosis is a rare neurodegenerative disorder of the upper motor neurons. Diagnostic criteria have changed considerably over the years, and the recent consensus criteria introduced 'probable PLS' for patients with a symptom duration of 2-4 years. The objective of this study is the systematic evaluation of clinical and neuroimaging characteristics in early PLS by studying a group of 'probable PLS patients' in comparison to a cohort of established PLS patients. METHODS: In a prospective neuroimaging study, thirty-nine patients were stratified by the new consensus criteria into 'probable' (symptom duration 2-4 years) or 'definite' PLS (symptom duration >4 years). Patients were evaluated with a standardised battery of clinical instruments (ALSFRS-r, Penn upper motor neuron score, the modified Ashworth spasticity scale), whole genome sequencing, and underwent structural and diffusion MRI. The imaging profile of the two PLS cohorts were contrasted to a dataset of 100 healthy controls. All 'probable PLS' patients subsequently fulfilled criteria for 'definite' PLS on longitudinal follow-up and none transitioned to develop ALS. RESULTS: PLS patients tested negative for known ALS- or HSP-associated mutations on whole genome sequencing. Despite their shorter symptom duration, 'probable PLS' patients already exhibited considerable functional disability, upper motor neuron disease burden and the majority of them required walking aids for safe ambulation. Their ALSFRS-r, UMN and modified Ashworth score means were 83%, 98% and 85% of the 'definite' group respectively. Motor cortex thickness was significantly reduced in both PLS groups in comparison to controls, but cortical changes were less widespread in 'probable' PLS on morphometric analyses. Corticospinal tract and corpus callosum metrics were relatively well preserved in the 'probable' group in contrast to the widespread white matter degeneration observed in the 'definite' group. CONCLUSIONS: Our clinical and radiological analyses support the recent introduction of the 'probable' PLS category, as this cohort already exhibits considerable disability and cerebral changes consistent with established PLS. Before the publication of the new consensus criteria, these patients would have not been diagnosed with PLS on the basis of their symptom duration despite their significant functional impairment and motor cortex atrophy. The introduction of this new category will facilitate earlier recruitment into clinical trials, and shorten the protracted diagnostic uncertainty the majority of PLS patients face.
Subject(s)
Amyotrophic Lateral Sclerosis , Motor Neuron Disease , Amyotrophic Lateral Sclerosis/diagnostic imaging , Humans , Motor Neuron Disease/diagnostic imaging , Motor Neurons , Neuroimaging , Prospective StudiesABSTRACT
PURPOSE: To describe 10 patients with Morbihan syndrome, a rare condition characterized by the slow appearance of erythema and solid edema on the upper portion of the face, and review the literature. METHODS: Retrospective case series and review. RESULTS: The majority of patients were male (80%), and the mean age at presentation was 67 years (range, 48-88 years); 60% had asymmetrical disease (affecting mainly the right side). All subjects underwent a lid biopsy to support the diagnosis of Morbihan syndrome, which showed features of inflammation and vascular dysfunction, highly suggestive of a rosacea histological picture complicated by chronic lymphoedema. A range of medical and surgical treatment were used with variable success. The most effective ones included oral isotretinoin, intralesional triamcinolone injections, and debulking surgery. CONCLUSIONS: Morbihan syndrome is a rare and chronic condition. It can be difficult to treat and may require a range of interventions.
Subject(s)
Rosacea , Aged , Aged, 80 and over , Erythema , Humans , Isotretinoin/therapeutic use , Male , Middle Aged , Retrospective Studies , United KingdomABSTRACT
OBJECTIVE: To describe a clinical entity of upper eyelid margin and meibomian gland inversion (MGI) sequential to meibomian gland dysfunction (MGD), in the absence of eyelash ptosis, trichiasis or manifest marginal entropion. We highlight its clinical features, surgical management and outcomes. METHODS: We performed a retrospective analysis of symptomatic MGI cases refractory to conservative management who underwent surgery in our centre over a 4-year period. Anatomical correction, resolution of symptoms and possible complications are reported. RESULTS: A total of 21 eyelids of 13 patients (mean age: 68.5 ± 15.4, range: 32-88 years) were analysed. Symptomatic MGI patients were operated only if they have noted immediate comfort when we corrected the lid margin position with a cotton tip. Those with refractory superior punctate corneal staining (n = 14 eyes), blink-related discomfort (n = 8) and pseudo-blepharospasm (n = 3) reported complete postoperative resolution. Milder symptoms showed partial improvement: gritty feeling (79%), sore eye (80%) and watery eye (86%). However, symptoms of dry eye disease (DED) persisted in 88% of patients. One case recurred in 6 weeks and was offered revision surgery. Median follow-up was 5 (range: 3-12) months. CONCLUSION: Meibomian gland inversion (MGI) is a subtle clinical entity that can be easily overlooked. Symptoms are often attributed to DED or MGD alone. It is likely that MGI represents early upper lid margin anatomical changes secondary to MGD before cicatricial marginal entropion becomes clinically apparent. Recommended treatment is conservative with intensive lid hygiene and topical MGD management. However, refractory symptomatic cases who respond positively to a 'cotton-tip test' (reversal of lid margin malposition with a rolling cotton-tip) may benefit from surgical intervention with favourable anatomical and functional outcome.
Subject(s)
Eyelids/surgery , Meibomian Gland Dysfunction/surgery , Meibomian Glands/surgery , Ophthalmologic Surgical Procedures/methods , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Meibomian Gland Dysfunction/diagnosis , Meibomian Glands/diagnostic imaging , Meibomian Glands/metabolism , Middle Aged , Retrospective Studies , Tears/metabolism , Treatment OutcomeABSTRACT
OBJECTIVES: Stenotrophomonas maltophilia is an opportunistic pathogen known to form biofilms on contact lens and case surfaces that may result in permanent visual loss in cases of microbial keratitis. Because of its multiple drug resistance and extremely low incidence, there is little consensus on treatment. We investigated the predisposing factors, management, and visual outcomes in a small case series of patients to better inform the management of this rarely reported keratitis. METHODS: Retrospective analysis of medical records was performed at a single tertiary referral center between 2011 and 2017. The case notes of each microbiology confirmed S. maltophilia keratitis were examined. RESULTS: Six cases were identified (four men) with a median age of 62 years (range 1 month-90 years) and pre-existing ocular surface disease in all cases. At presentation, four patients were using bandage contact lenses and three were on topical antibiotic and steroid medications. Initial antibiotic treatment was intensive topical 0.3% ofloxacin and 5% cefuroxime, which was modified based on corneal scrape culture and sensitivity and clinical findings. One patient chose not to complete the treatment course. The 5 remaining patients had complete resolution of ulceration over a mean of 2.9 months (SD 0.8 months). CONCLUSIONS: Contact lens in the context of ocular surface problems, prolonged topical antibiotic and steroid treatments may predispose to S. maltophilia, a rare cause of keratitis. We report successful treatment with case-specific combinations of topical antibiotics such as fluoroquinolone, cotrimoxazole, and/or cephalosporin agents, although visual outcomes remain poor due to corneal scar.