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Neurology Update. Paul Hart Neurologist Epsom + St Helier AMNU @ St George’s Royal Marsden Hospital. Neurology Update. Diseases Parkinsons disease Multiple Sclerosis Epilepsy Stroke Dementia Headache ……. Neurology Update. Diseases Parkinsons disease Multiple Sclerosis Epilepsy

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Neurology Update


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    1. Neurology Update Paul Hart Neurologist Epsom + St Helier AMNU @ St George’s Royal Marsden Hospital

    2. Neurology Update • Diseases • Parkinsons disease • Multiple Sclerosis • Epilepsy • Stroke • Dementia • Headache • ……..

    3. Neurology Update • Diseases • Parkinsons disease • Multiple Sclerosis • Epilepsy • Stroke • Dementia • Headache • …….. Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis Neuromuscul Disord. 1999 Jun;9(4):232-8

    4. Neurology Update • Diseases • Parkinsons disease • Multiple Sclerosis • Epilepsy • Stroke • Dementia • Headache • …….. Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis Neuromuscul Disord. 1999 Jun;9(4):232-8 • Neurology Top 10 Tips • Services • TWRs • Direct access investigations • Local provision • How to get the most out of your neurologist

    5. Update - Parkinsons disease • Suspected PD • Unsuspected PD – making the penny drop • PD review • Common • Increasing prevalence • Predicted to treble over the next 50 years • Age 50 – 10:100,000 • Age 80 – 200:100,000 • < 80% confirmed at post-mortem !?

    6. Akinetic Idiopathic Parkinsons Disease Parkinsons plus MSA PSP DLB CBD Secondary Parkinsonism Hyperkinetic Chorea Ballism Tremors Myoclonus Wilsons disease Dystonia Tics + Tourettes Sleep related movement disorders Ataxia Dyskinesias Psychogenic Classification of Movement Disorders

    7. Definition of idiopathic PD • Pathological diagnosis • depigmentation + neuronal loss in substantia nigra • Intraneuronal inclusions- Lewy bodies

    8. Tremor UL>LL Asymmetric Rest tremor Tongue lips chin Rigidity Akinesia Postural instability Gait micrographia Facial Hypomimia Speech Non-motor manifestations Constipation EDS Anosmia REM behaviour disorder Depression Dementia Pain Postural stability Skin Autonomic …. Clinical Features

    9. Sleep • 75-90% PD sleep dysfunction • Insomnia • Sleep fragmentation • Sleep akinesia • Nocturia • Nocturnal panic attacks • RLS • Excesssive daytime somnolence • Drug induced psychosis 10-30% • reduce parkinson meds • monitor response • neuroleptic trial quetiapine / clozapine / olanzapine • Mirtazapine • RIvastigmine Neuropsychiatric problems Depression and Dementia

    10. A Clinical Diagnosis Investigations: Exclude Wilsons -young with tremor MRI DaT scan Research SPECT PET

    11. Essential Tremor Kinetic +/- postural tremor 4-12 Hz UL, head, voice, LL, trunk, tongue >90% undiagnosed 73% report significant disability Treatment: medical, botox, surgical Parkinsons plus MSA PSP LBD CBD Drug induced Parkinsonism 12% of 328 patients referred to secondary care Prochloperazine 32% Typical antipsychotics 42% atypical antipsychotics 18% Metoclopramide 11% Amiodarone 8% Lithium 8% Antihistamines 8% Promethazine and cinnarazine Valproate 5% PD - Is it something else ?

    12. PD Treatment – what when and how? • 1817 James Parkinson • Blood letting • Iatrogenic pus formation • 2011 Dopaminergic • Non dopaminergic • Symptomatic • Neuroprotective • Surgery – Ablation – DBS – Brain Grafting • Preventative

    13. Levo Dopa (DATATOP trial n=352; F/U 20 months +/- 9) • Wearing off 50% • Dyskinesias 33% • Severe on-off 10% • Hedonistic homeostatic dysregulation • Pros: effective • Cons: side effects • Early side effects – N+V, HR, BP • Late SE • motor fluctuations • dyskinesias • neuropsychiatric • Symptoms unresponsive to L-Dopa • postural instability • freezing phenomena • speech • sialorrhoea • depression and dementia • ANS - sweating, urinary frequency, constipation • sensory symptoms + pain • Tremor • REM sleep behaviour disorder

    14. Levodopa therapeutic manoeuvres • On with dyskinesia vs Off without dyskinesia • CR preparations • Hyperfractionate dosing schedule • COMT inhibitors - entacapone, tolcapone • Stalevo • Levodopa carbidopa entacapone • 50 / 12.5 / 200 • Stalevo “50” “75” “100” “125” “150” “200” • MAO inhibitors - selegeline, rasagiline • Amantadine • Dopamine Agonists • Duo-dopa • Apomorphine pump

    15. No dyskinesia potentially neuroprotective delays use of levodopa longer half life no absorption delay/dietary effects no metabolic conversion Apomorphine Pergolide Cabergoline Pramipexole Ropinirole Rotigitone Side effects Ankle oedema Gambling Sexual appetite Agonists

    16. PD – whats new • Genetics • Drugs • NSAIDs • Ibuprofen protective but not other NSIADs • N=136,474 • Stem cells

    17. PD – whats new - Genetics • 15% PD patients have an affected 1st degree relative • 5% due to mutation in one of several specific genes • alpha-synuclein (SNCA) • ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) • parkin (PRKN) • leucine-rich repeat kinase 2 (LRRK2 or dardarin) • PTEN-induced putative kinase 1 (PINK1) • DJ-1 • ATP13A2 • In most cases, people with these mutations will develop PD. • All rare except LRRK2 • 10% familial PD • 3% sporadic PD • Genome wide association studies • Complex late onset sporadic degenerative • 15 confirmed genes • Mutations in genes including SNCA, LRRK2 and glucocerebrosidase (GBA) have been found to be risk factors for sporadic PD. • Mutations in GBA are known to cause Gaucher's disease • All identified risks account for 2.5-3x risk

    18. Update – Multiple Sclerosis

    19. Update – Multiple Sclerosis • Disease modifying therapies • CCSVI • Lifestyle effects • Sativex • NMO antibodies

    20. Refresher Demyelination Inflammation Clinically isolated syndrome Optic neuritis Transverse myelitis Brain stem motor Sensory McDonald criteria 2001 2005 2010 Update – Multiple Sclerosis

    21. McDonald criteria Clinical presentationAdditional data needed for MS diagnosis • Two or more attacks objective clinical evidence of two or more lesions None • Two or more attacks objective clinical evidence of one lesion Dissemination in space shown on MRIor Up to two MRI detected lesions typical of MS plus positive CSF*or Await a further relapse suggestive of dissemination in space (ie affecting another part of the body) • One attack objective clinical evidence of two or more lesions Dissemination in time demonstrated by MRIor Second clinical attack (relapse) • One attack objective clinical evidence of one lesion (known as 'clinically isolated syndrome') Dissemination in space demonstrated by MRIor Up to two MRI detected lesions typical of MS plus positive CSF AND dissemination in time demonstrated by MRIor Dissemination in time demonstrated by MRI (ie new lesion seen on MRI at least 3 months after the original scan)or Second clinical attack (relapse) • Insidious neurological progression suggestive of multiple sclerosis (typical for primary progressive MS) Positive cerebrospinal fluid* AND dissemination in space, shown on MRI or Abnormal visual evoked potential plus abnormal MRI AND dissemination in time demonstrated by MRI or Continued progression for one year (determined retrospectively or by ongoing observation)

    22. Treatment of MS Relapses Treatment Oral methyprednisilone 500mg od - 5days Prevention DMTs Treatment of symptoms Fatigue Amantadine Modafinil Depression Spasticity Baclofen Tizanidine Sativex Bladder Etc…. Multi-disciplinary care Update – Multiple Sclerosis

    23. Update – Multiple Sclerosis - DMTs • a group of compounds which alter the progression of MS • reduce the frequency and severity of relapses and slow the development of disability in some people. • Beta interferon 1a AVONEX im REBIF sc 1b BETAFERON sc Fingolimod po • Glatiramer acetate COPAXONE sc • Different mechanism, similar effect • Natalizumab TYSABRI • A recombinant humanised monoclonal antibody produced in murine myeloma cells. • The specific mechanism(s) not fully defined. However, inhibition of leucocyte transmigration out of the vascular space. • Progressive Multifocal Leukoencephalopathy*(PML) is an opportunistic infection caused by the JC virus that typically occurs in patients that are immunocomprimised. • Mitoxantrone • Cardiac toxicity

    24. Update – Multiple Sclerosis - DMTs • CCSVI • Zamboni • Stem cells • Lifestyle effects • Vitamin D • tobacco • diet • NMO antibodies • Neuromyelitis optica (Devic’s disease) • Aquaporin antibodies

    25. Update – Multiple Sclerosis - DMTs • CCSVI • Zamboni • Stem cells • Lifestyle effects • Vitamin D • tobacco • diet • NMO antibodies • Neuromyelitis optica (Devic’s disease) • Aquaporin antibodies • Other neurological antibodies • MUSK • VGKC • NMDA

    26. Update – Epilepsy • More New AEDs • Enhance slow activation of Na channels • Lacosamide • Rufinamide • Ca channel lockers + carbonic anhydrase inhibitor • Zonisamide • Sudden unexplained death in epilepsy • Epilepsy SMR 1.6-9.3 • Underlying disorder / status / accidents / suicide / Rx related death / SUDEP • 8-17% of deaths • Memory • Psychosocial

    27. Update – Stroke • Risk of stroke after TIA • Thrombolysis • PFO

    28. Update – ……

    29. Overview • Neurology - there’s a lot of it about

    30. Overview • Neurology - there’s a lot of it about • Guidelines, QOFs, and more guidelines

    31. Overview • Neurology - there’s a lot of it about • Guidelines, QOFs, and more guidelines • Do you suffer from Neurophobia ?

    32. Overview • There’s a lot of it about • Guidelines, QOFs, and more guidelines • Neurophobia widespread

    33. Neurological disorders are common • WHO “Neurological disorders – a public health challenge” “one of the greatest threats to public health” • Mortality vs DALYs • Neurological disease accounts for 20% of admissions to general hospitals • More diagnoses than the rest of medicine put together

    34. Guidelines, QOFs, etc….. • NICE – PD • NICE – epilepsy • SIGN – epilepsy • QOF – epilepsy • Stroke and TIA • Headache • MS • And all the others….

    35. Do you suffer from Neurophobia ? • A fear of neurosciences and clinical neurology • Jozefowicz 1994 • Schon Hart et al 2002

    36. Do you suffer from Neurophobia ? • A fear of neurosciences and clinical neurology • Jozefowicz 1994 • Schon Hart et al 2002 • Seeds Sown at medical school ?

    37. We can cure it for you ! • The Epsom and St Helier neurology Service • ~100% patients seen by Consultant grade • 4 Consultant Neurologists • 2 Consultant Neurophysiologists • 4 specialist nurses • Neuro PT, OT etc… • State of the art imaging facilities, EEG, EMG, PIU • 52 clinics per month • 94% of ward referrals seen on day of referral, 99% within 48 hrs

    38. Neurology – top ten tips • TIAs never cause isolated loss of consciousness • Numb tingling hands are rarely due to neck pathology • Beware of medication overuse headache • Essential hypertension, sinusitis and “eye strain do not cause chronic daily headache • Vertigo usually originates from the vestibular apparatus not the brain • Diplopia – monocular = ophthalmology, binocular = neurology • Know which headaches are worth worrying about • Beware of misdiagnosing tremor • Radiological imaging is rarely helpful in illuminating headache or back pain • The neurological examination is hugely overvalued in non-neurologists

    39. Our ethos ? • Referral guidelines ? • Communication • Tel 0208 296 3355 • Fax 0208 296 3356

    40. Neurology Update Paul Hart Neurologist Epsom + St Helier t 0208 296 3355 f 0208 296 3356 AMNU @ St George’s Royal Marsden Hospital