Objective To analyse data from two previously published individual studies and two meta-analyses of the Ascertain Dementia 8 (AD8) cognitive screening instrument to calculate the recently described ‘likelihood to be diagnosed or misdiagnosed’ (LDM) metric, the ratio of ‘number needed to misdiagnose’ (NNM = 1/Inaccuracy) to either ‘number needed to diagnose’ (NND = 1/Youden index) or ‘number needed to predict’ (NNP = 1/predictive summary index). Results Raw data (true positives and negatives, false positives and negatives) were extracted and LDM values for the diagnosis of dementia were calculated. For the individual studies (n=212, 67 respectively) LDM values were all <1, favouring misdiagnosis, whereas for the meta-analyses (n=3278, 3694 respectively) all LDM values were >1, favouring diagnosis. This discrepancy may be explained by the poor specificity of AD8 in the individual studies, lower than in any other study included in the meta-analyses, giving very high values for NND and NNP and lower values of NNM than in the meta-analytic data. This may relate to differences in casemix between the various studies. Conclusion LDM is an easily calculated and potentially useful test metric. LDM values derived from meta-analytic data may differ from those of individual test accuracy studies.
Background: Epilepsy is a common, serious neurological condition affecting over 50 million people worldwide. Approximately 70% of those with epilepsy will be rendered seizure-free with a first or second appropriate anti-seizure medication. The remaining 30% of individuals are refractory to medications despite ongoing advances in the pharmacological armamentarium. In people with drug resistant focal epilepsy, particularly those with substrates for seizures identifiable on brain imaging, the most effective treatment is resective surgery. Whilst the importance of progressing those with drug resistant focal epilepsy through an epilepsy surgery programme is clinically accepted, the cost-effectiveness of this approach is uncertain. Therefore, in developing the current National Institute of Health and Care Excellence (NICE) Guidelines on Epilepsies in children, young people and adults (NG217), we conducted a cost utility analysis of resective epilepsy surgery in adults.Methods: Data were obtained from UK epilepsy surgery centres to evaluate the costs of pre-operative assessment. A de-novo decision analytic model, comprising of a one-year decision tree and life-time Markov model, compared resective epilepsy surgery to medical management from a national healthcare and personal social services perspective. According to NICE pre-requisites, an incremental cost-effectiveness ratio (ICER) below £20,000 cost per Quality Adjusted Life Year (QALY) was considered cost effective.Findings: Data from 762 patients informed pre-operative evaluation costs, which were £8,182 per person on average. The total lifetime cost of epilepsy treatment for people that had surgical treatment was £56,911, compared with £32,490 for medical management. Total QALYs per person for surgery were 15·91 and 13.76 for medical management. Resective epilepsy surgery was shown to be cost effective with an ICER of £11,348 per QALY gained.Interpretations: The study informs and strengthens recommendations to prioritise referral of those with drug refractory epilepsy to surgical centres, providing economic rationale for development and support of resective epilepsy surgery programs across national healthcare systems.Funding: This work was integral to the development of the Guideline on Epilepsies in children, young people and adults (NG217) by the National Institute for Health and Care Excellence (NICE), which is an executive non-departmental public body of the Department of Health and Social Care in England.Declaration of Interest: The authors declare no direct conflicts of interest.Ethical Approval: All data here collected were obtained as part of development of the National Institute of Health and Care Excellence (NICE) guideline on 'Epilepsies in children, young people and adults (NG217)'. Where applicable, analysis was performed on aggregated, anonymised data
Facial onset sensory motor neuronopathy (FOSMN) is a rare, slowly progressive bulbar onset motor and sensory neuronopathy. Described only in 2006, it is still under–recognised with fewer than 20 cases reported in world literature. Although there are marked similarities to classical bulbar onset MND, FOSMN is set apart clinically by the striking facial–onset sensory deficits with subsequent development of motor deficits, slow evolution in a rostral–caudal direction and a much better prognosis.
Methods
We present three cases from three different regions of the UK. Case 2 was presented at ABN 2011. A 62–year–old man presented with a three–year history of perioral paraesthesia, numbness and slurred speech, followed by upper limb weakness, fasciculations and muscle cramps. He was dysarthric, anosmic and anegusic. Sensation to pin prick and fine touch was decreased in all divisions of the trigeminal nerve bilaterally with absent corneal reflexes bilaterally. The tongue was atrophic; fasciculations were noted in the tongue and the upper limbs. Electrophysiological studies revealed widespread neurogenic changes without evidence of polyneuropathy. Extensive investigations for alternative aetiologies were unyielding. A 38–year–old woman presented with bilateral facial sensory loss. Over the following ten years she developed weakness and sensory loss in her arms and legs. Fasciculations and flaccid weakness were noted throughout her upper limbs, and there was finger drop of her fourth and fifth digits. Sensation to pinprick was reduced in her face, upper trunk and arms with some involvement distally in the legs. Proprioception and vibration sensation was normal. Horizontal saccades were slow. Electrophysiological studies revealed widespread denervation. No alternate aetiology was found on extensive testing. There was no response to repeated courses of intravenous immunoglobulin over 12 months. A 69–year–old man presented with a four–month history of numbness affecting his left cheek gradually progressing to involve his right cheek, jaw, forehead and tongue. Speech was dysarthric with reduced sensation to pinprick and soft touch in all divisions of the trigeminal nerve as well as the tongue. Over the next five years he developed wasting and fasciculations of his tongue with widespread wasting and brisk reflexes of the upper limb muscles. No alternate aetiology was detected after extensive tests. Treatment with steroids and subsequently with intravenous immunoglobulin was of no benefit.
Conclusions
These three cases are similar to previously published reports and support the hypothesis that FOSMN is a sporadic, degenerative disorder distinct from typical MND.1 TDP–43 mutations were reported by some but are not universally present. Early, accurate diagnosis is essential to allow appropriate counselling regarding the prognosis, which is much better than for bulbar onset MND with survival often exceeding ten years.
A 28 year old woman of Pakistani origin, who was 18 weeks pregnant, presented with a four week history of dry cough, breathlessness, and intermittent wheeze. Antibiotics and inhaled bronchodilators had been prescribed with no improvement in symptoms. She was a never smoker and drank no alcohol. Six years previously she had been treated for smear and culture positive, fully sensitive, pulmonary tuberculosis. After this she had developed a right-sided pneumothorax, which resolved after insertion of an intercostal chest drain. She had no history of pre-existing airways disease. On examination she was able to talk in full sentences, she had a normal temperature but was tachypnoeic, with a respiratory rate of 24 breaths/min and oxygen saturation of 91% on room air. Respiratory examination showed scattered wheeze throughout. Her pulse was 74 beats/min and blood pressure was 103/71 mm Hg. The rest of the cardiovascular examination was normal. Abdominal examination was consistent with 18 weeks of pregnancy. Arterial blood gases on room air showed mild hypoxia, with partial pressure of oxygen at 7.98 kPa. Peak expiratory flow rate on admission was 150 L/min. Spirometry (done at a later date when she was clinically stable) showed a forced expiratory volume in one second of 0.89 L (34% of predicted). A chest radiograph was performed (fig 1⇓), followed by bronchoscopy, which showed a necrotic tumour in the right upper lobe.
Abstract Background Patients with chronic focal epilepsy may have atrophy of brain structures important for the generation and maintenance of seizures. However, little research has been conducted in patients with newly diagnosed focal epilepsy (NDfE), despite it being a crucial point in time for understanding the underlying biology of the disorder. We aimed to determine whether patients with NDfE show evidence of volumetric abnormalities of subcortical structures. Methods Eighty-two patients with NDfE and 40 healthy controls underwent MRI scanning using a standard clinical protocol. Volume estimation of the left and right hippocampus, thalamus, caudate nucleus, putamen and cerebral hemisphere was performed for all participants and normalised to whole brain volume. Volumes lower than two standard deviations below the control mean were considered abnormal. Volumes were analysed with respect to patient clinical characteristics, including treatment outcome 12 months after diagnosis. Results Volume of the left hippocampus ( P (FDR-corr) = 0.04) and left ( P (FDR-corr) = 0.002) and right ( P (FDR-corr) = 0.04) thalamus were significantly smaller in patients relative to controls. Relative to the normal volume limits in controls, 11% individual patients had left hippocampal atrophy, 17% had left thalamic atrophy and 9% had right thalamic atrophy. We did not find evidence of a relationship between volumes and future seizure control or with other clinical characteristics of epilepsy. Conclusions Volumetric abnormalities of structures known to be important for the generation and maintenance of focal seizures are established at the time of epilepsy diagnosis and are not necessarily a result of the chronicity of the disorder.
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