The West of England Seminars in Advanced Neurology (WESAN) holds annually in Exeter. Each year 13 invited speakers talk on practical and topical neurological issues, and the delegates consist of neurology trainees and consultants.
The first talk this year, ‘My approach to diagnosing tremor in clinic’, was presented by Jane Alty, Consultant Neurologist at Leeds Teaching Hospitals NHS Trust. It was an interactive talk with lots of audience participation. She presented very interesting videos highlighting the characteristic features of the different common tremor syndromes. She described the new essential tremor (ET) diagnostic criteria and the examination features and activating manouevres which distinguish it from other tremors. She showed the differences between ET and a re-emergent postural tremor of Parkinson’s disease (PD). She pointed out that, unlike with dystonia, ET does not present with isolated head tremor. She highlighted other distinguishing features of dystonic tremor such as thumb tremor, fluctuation with certain postures and actions, and focal muscle hypertrophy. She presented interesting video cases of an isolated shaving tremor, a snooker-player tremor, and also functional tremors (which are characterized by variability and entrainment). She also explored the differential diagnoses of tremor such as myoclonus, dyskinesia and tics.
‘The spectrum of IgG4 antibody disorders in neurology’ was the title of the presentation by Burden Professor of Neurology, Neil Scolding. He illustrated his talk with the case of a male construction worker who developed diverse neurological features including multiple cranial neuropathies. He emphasised the value of repeated tissue biopsy in making the diagnosis of IgG4 antibody disorders and other cryptic neurological diseases. He illustrated the multi-systemic nature of IgG4 antibody disorders by reviewing its varied manifestations such as retroperitoneal fibrosis, pancreatitis, interstitial lung disease, and Reidel’s thyroiditis. He also pointed out the frequent association of IgG4 antibody disorders with allergy and atopy. He reflected on the observation that affected patients are usually middle aged, ‘blue collar’, males whose outdoor occupations may increase their risk of acquiring the disorder. He emphasised that neurological manifestations of IgG4 antibody disorders are relatively rare, and the characteristic features are hypertrophic pachymeningitis, hypophysitis, and orbital involvement. He reviewed the major differential diagnoses of chronic meningitis, and he explored the requirement for long-term immunosuppressive therapy with agents such as azathioprine and rituximab. He concluded by pointing out that IgG4 antibodies are also detected in other neurological disorders such as NF155 chronic inflammatory demyelinating polyneuropathy (CIDP), anti-MUSK myasthenia gravis, and LGI1 limbic encephalitis.
Jasper Morrow, Consultant Neurologist at the National Hospital for Neurology at Neurosurgery presented ‘The role of MRI in muscle disorders’. His talk focused on the use of MRI in confirming muscle involvement, guiding the site of muscle biopsy, and directing genetic testing. He presented several cases to illustrate the recognisable imaging patterns of several muscle diseases; these features include bilateral atrophy of the trapezius muscles in facioscapulohumeral muscular dystrophy (FSHD), and central gastrocnemius muscle stripe in myotonia congenita. He reviewed the utility of MRI in monitoring disease progression and in assessing response to treatment, particularly of inflammatory myopathies and muscle channelopathies. He showed how MRI may identify neurogenic diseases such as BICD2 gene mutation which manifests with islands of preserved muscle.
The fourth talk, ‘Innovations in brain tumour management’, was presented by Katia Cikurel, Consultant Neurologist at King’s College Hospital. She began with an elaboration of the latest classification of brain tumours, and she explored recent progress in management, particularly the evolution of multidisciplinary patient care. She said brain tumour treatment is now guided by the Stupp protocol, and she reviewed the strong evidence showing that brain tumour survival is closely associated with extent of tumour resection. She discussed other advances such as the fluorescent dye, gliolan, the benefits of awake craniotomy, and the use of intra operative monitoring. She illustrated the improved outcomes arising from the use of adjuvant temozolamide and intensity modulated radiotherapy. She highlighted the use of MGMT methylation status in predicting response to chemotherapy; IDH positivity in predicting better prognoses; and ATRX in predicting poor chemosensitivity and faster tumour progression with astrocytomas. She highlighted the importance of close monitoring of low grade gliomas with a view to early intervention with radiotherapy and chemotherapy. She discussed the management of tumour-related epilepsy pointing out that prophylactic anti-epileptic drugs (AEDs) are not indicated, and non-enzyme inducing AEDs should be considered after the first seizure. She pointed out the benefit of radiotherapy in controlling resistant seizures, and she discussed the prospects of the on-going study into dendritic cell (DC) vaccines for malignant gliomas.
Howard Faulkner, Consultant Neurologist at Bristol, presented on ‘Epilepsy surgery: when and why?’ He started by describing drug resistant epilepsy as the failure of two tolerated and appropriately chosen AEDs. He pointed out that the increasing number of new AEDs has not impacted on the rate of drug resistant epilepsy, which remains about 33%. He noted that epilepsy surgery is usually performed in subjects with lesions on imaging but 40-60% of patients with non-lesional epilepsy may also be seizure free after surgery. He discussed the protocol for selecting patients for epilepsy surgery and illustrated the importance of video-EEG in confirming the diagnosis and refuting misdiagnoses such as functional seizures and cardiogenic disorders. He discussed the use of SPECT scans to localise the seizure onset in non-lesional cases and invasive EEG techniques, using depth electrodes and robotic stereo EEG, to establish surgical targets. He listed the diverse benefits of epilepsy surgery beyond seizure freedom such as increased quality of life and reduced health care costs. He ended by discussing the role and technique of vagus nerve stimulation (VNS) where resective surgery is not possible with which 50% of subjects on VNS will achieve a 50% reduction in seizure frequency.
‘Neuropsychiatry and the borderzone with neurology’ was the title of the talk by Andrea Cavanna, Consultant in Behavioural Neurology at the National Centre for Mental Health, Birmingham. He started with a review of the mind-brain dichotomy and the neuroanatomical substrates which play a role in behavioral Neurology. He made extensive historical references to leading figures in the field such as Stanley Cobb, Alexander Luria, Oliver Sacks, Harold Klawans, Adam Zeman, and Suzanne O’Sullivan. He explored the relationship between consciousness and neurological disorders such as epilepsy. He discussed the emotional manifestations of seizures and highlighted the psychiatric comorbidities of epilepsy such as personality disorders, schizophrenia, hypereligiosity, and hypergraphia. He reviewed the behavioural spectrum of Tourette’s syndrome such as obsessive compulsive disorders (OCD), attention deficit hyperactivity disorder (ADHD), and affect dysregulation. He explored the concept of the triune brain and he used the case of Phineas Gage to demonstrate that severe traumatic brain injury may manifest only with personality and psychiatric disorders, without any physical neurological deficits.
The last presentation of the first day was by Pooja Dassan, Consultant Neurologist at Imperial College Healthcare Trust, and it was titled ‘A practical approach to neurological problems in pregnancy’. Her wide-ranging presentation started with headache in pregnancy. She said migraine is the most frequent cause of headache in pregnancy, and she reviewed the migraine drugs that are safe to use in pregnancy. She discussed reversible cerebral vasoconstriction syndrome (RCVS), which usually manifests post-partum, and which exhibits a beading appearance on angiography. She listed other headache syndromes relevant to pregnancy such as posterior reversible encephalopathy syndrome (PRES), and cerebral vein thrombosis (CVT). She discussed idiopathic intracranial hypertension (IIH), noting the relative safety of acetazolamide after the first trimester, and the possible teratogenic risk of high dose frusemide. In discussing epilepsy, she emphasised the importance of pre-conception counselling, and recommended pre-conception folic acid. She emphasised the importance of regular monitoring of lamotrigine levels in pregnancy, and pointed out that levels of levetiracetam, but not carbamazepine, also decrease significantly in pregnancy. She reviewed the emerging consensus guidelines on the management of multiple sclerosis (MS) in pregnancy with emphasis on the safety of disease modifying treatments (DMTs). She emphasised that fingolimod and teriflunomide are contraindicated in pregnancy but the benefits of interferons, glatiramer and natalizumab may outweigh their risks. She finally reviewed the safety of imaging in pregnancy, pointing out that CT, with or without contrast, would not be contraindicated but only non-contrast MRI should be performed.
The second day was kicked off by Sybil Stacpoole, Consultant Neurologist at Peterborough and Addenbrooke’s Hospitals, whose topic was ‘Resolving the diagnostic and management dilemmas in multiple sclerosis’. She reviewed the current diagnostic criteria for multiple sclerosis, noting the inclusion of cortical lesions and oligoclonal bands. She reminded us that paroxysmal symptoms lasting more than 24 hours fulfil the definition of relapses, although a diagnosis cannot be based on a single paroxysmal episode. She discussed the surveillance of people who have non-diagnostic features on brain imaging, advising at least a two-year follow-up. She reviewed the NHS England treatment algorithm noting that alemtuzumab and dimethylfumarate are often the first line options, and that the use of cladribine and all higher potency disease modifying therapies (DMTs) now requires approval of a multidisciplinary team (MDT). She noted that fingolimod is only used if another DMT fails, and copaxone is an appropriate option if pregnancy is a current consideration. She discussed risk stratification data which suggest that brain stem lesions, multiple lesions, and contrast enhancement portend a poor outcome. She discussed the monitoring protocols for the different DMTs, and the natalizumab risk stratification for progressive multifocal leukoencephalopathy (PML). She reviewed the uncertainties surrounding when and how to stop DMTs, and the uncertain benefit of ocrelizumab in primary progressive MS (PPMS). She emphasized the need for the field to work together to develop meaningful national data collection, to enhance both efficacy and safety knowledge, similar to the systems that oncology and rheumatology seem to have achieved.
Alexander Rossor, Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, presented ‘My approach to the hereditary neuropathies’. He began by describing the classical presentation of Charcot Marie Tooth disease (CMT) and discussing the commonest type, CMT1A, which is typically demyelinating and sensorimotor, and which demonstrates homogeneous slowing of nerve conduction velocity; (helping to distinguish it from acquired demyelinating neuropathies). He then reviewed the axonal hereditary neuropathies, particularly CMT2, hereditary motor neuropathy (HMN), and hereditary sensory neuropathy (HSN). He said MFN2 and MORC2 gene mutations are the commonest cause of CMT2. He recommended testing for PMP22 duplication before proceeding to gene panel testing if the neuropathy is demyelinating, and requesting panel testing directly if it is axonal. He pointed out the uncertainty of confirming that a specific mutation is pathogenic, but said the diagnostic certainty may be improved by phenotyping, family segregation, absence in controls, and predictive programmes. He discussed hereditary neuropathy with liability to pressure palsies (HNPP), advising against routine carpal tunnel release in this disorder, and emphasizing the increased risk of nerve palsy with anaesthetic positioning. He pointed out that CMTX may present with a split hand pattern of hand muscle atrophy, and CMT1D may present with vocal cord palsy. In reviewing amyloid neuropathy, he highlighted the sensitivity of SAP scans for AL Amyloid, and TcDPD scans for familial amyloid polyneuropathy (FAP). He said FAP often presents with an aggressive short history and may mimic CIDP. He discussed the conventional treatments of hereditary neuropathies including orthoses and surgery, and he reviewed emerging drug therapies such as antisense oligonucleotides, and baclofen/sorbitol/naltrexone combination for CMTIA.
‘How I manage the patient with difficult idiopathic intracranial hypertension’ was the title of the presentation by Alexandra Sinclair who runs the multidisciplinary IIH service at University Hospital, Birmingham. She started by reviewing the pathogenesis of IIH, emphasising the role of arachnoid granulations and the glymphatic drainage system. She discussed the similar clinical features and exacerbating factors of IIH and migraine, and she highlighted the difficulty in distinguishing papilledema from pseudopapilledema, a frequent cause of misdiagnosis of IIH. She reviewed the latest IIH guidelines which recommend urgent imaging and venography within 24 hours of detecting papilledema. Discussing the role of lumbar puncture (LP) in the diagnosis of IIH, she noted that an opening pressure of 25-30mmHg is a grey zone and may be normal if there are no other features of IIH. She pointed out that improvement of headache following LP does not confirm IIH because 23% of people with non-IIH headaches also report improvement. Discussing the medical treatment of IIH, she noted that 48% of subjects on acetazolamide discontinue it because of side effects, and topiramate may be as effective as acetazolamide. She emphasised that serial lumbar punctures are not recommended for IIH. She reviewed the surgical treatments of IIH, usually shunting procedures, which are required in about 8% of cases. She emphasised that CSF diversion procedures are not indicated for the treatment of headache but to prevent visual loss. She said there is no requirement for shunt revisions unless there is visual deterioration. She discussed the uncertain benefit of neurovascular stenting, and she reviewed the emerging drug treatments for IIH such as 11beta HSD1 inhibitors and GLP-1receptor agonists. She discussed the IIH Weight Study which is currently investigating the therapeutic value of weight loss.
Anne Rosser, Professor of Clinical Neuroscience at Cardiff University, presented several videos to illustrate her talk, ‘Huntington’s disease: spectrum and treatment prospects’. She reviewed the motor phenotype of HD which includes apraxia, bradykinesia, impairment of balance, and orolingual dyskinesia. She emphasised that chorea is not a universal feature of HD. She discussed the cognitive profile of HD which has dysexecutive, social, and linguistic manifestations. She also noted that cognitive impairment is more predictive of future loss of independence in HD than the motor features. She reviewed the behavioural manifestations of HD which include apathy, irritability and perseveration. She also discussed the psychiatric symptoms, noting that depression and anxiety are often intermittent, whilst delusions and hallucinations are rare. She reviewed the treatment of HD, explaining the move away from treating chorea unless it is severe or disabling. She highlighted the importance of physical therapy in improving function and noted that the course of HD is relentlessly progressive over 20 years. She reviewed the emerging therapies of HD including gene silencing using antisense oligonucleotides (ASO), and cell replacement therapy of the striatal medium spiny neurons.
Charlotte Dawson, Consultant in Metabolic Medicine at Queen Elizabeth Hospital Birmingham, presented case reports to illustrate her talk on ‘Acute neurological presentations of inherited metabolic disorders’. The first case report was of homocystinuria manifesting as venous sinus thrombosis. The second case was of Fabry disease presenting as young stroke. She recommended testing for Fabry disease in people with a family or personal history of unexplained cardiomyopathy and/or renal disease. She discussed the diverse clinical features of Fabry disease including heat and cold intolerance and IBS-like symptoms. Her third case was of the urea cycle disorder ornithine transcarbamylase (OTC) deficiency, which presents with recurrent hyperammonaemic encephalopathy. She noted that advanced liver disease is the commonest cause of hyperammonaemic encephalopathy, but that alcohol excess, malnutrition and prolonged fast e.g. perioperatively can unmask previously undiagnosed OTC. She discussed the recommended investigations such as organic acids, plasma amino acids, and mutation analysis, and she reviewed the treatment with ammonia-scavenging drugs. The fourth case is of metabolic myopathy, pointing out that the commonest causes in adults are CPT2 deficiency and McArdle’s disease. She highlighted the presentation with rhabdomyolysis, and the frequent triggers such as unaccustomed exercise and fasting.
The last talk of the course was presented by Jenny Vaughan, Consultant Neurologist at Imperial College Healthcare Trust, and it was titled ‘Call the neurologist! Delivering doctors from lawyers in 21st century Britain’. Her presentation was on the investigation of doctors for the crime of gross negligence manslaughter (GNM). She pointed out that 90% of doctors investigated for GNM are not prosecuted, and black and ethnic minority doctors seem to be disproportionately investigated. She discussed her personal involvement in two recent key legal cases. She first reviewed the timeline of the prosecution, tragic conviction, and eventual successful appeal of surgeon David Sellu for GNM. She detailed the errors that resulted in his conviction, including how expert witnesses usurped the role of the jury. She explained how forensic analysis of the case and crowd-funding helped to overturn his conviction in 2016. She then reviewed the case of Hadiza Bawa-Garba, the paediatrics trainee whose conviction for GNM was also overturned on appeal. She explored the factors, including her written personal reflections, which contributed to her conviction. She discussed the systemic factors and human errors that led to the death of the patient involved in the case, and the varied mitigating circumstances that should have been considered from the outset. She ended with a discussion of human errors, including a helpful and relevant classification of unsafe acts into intentional and unintentional types.
WESAN 2019 is scheduled to hold on 21-22 November 2019. For updates, please check the WESAN website www.wesan.org.uk
