Neurology Update

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Neurology Update

• Paul Hart
• Neurologist
• Epsom St Helier
• AMNU _at_ St Georges
• Royal Marsden Hospital

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Neurology Update

• Diseases
• Parkinsons disease
• Multiple Sclerosis
• Epilepsy
• Stroke
• Dementia
• Headache
• ..

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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 Jun9(4)232-8

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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 Jun9(4)232-8
• Neurology Top 10 Tips
• Services
• TWRs
• Direct access investigations
• Local provision
• How to get the most out of your neurologist

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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 10100,000
• Age 80 200100,000
• lt 80 confirmed at post-mortem !?

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Classification of Movement Disorders

• 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

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Definition of idiopathic PD

• Pathological diagnosis
• depigmentation neuronal loss in substantia
  nigra
• Intraneuronal inclusions- Lewy bodies

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Clinical Features

• Tremor
• ULgtLL
• 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
• .

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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
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A Clinical Diagnosis

• Investigations Exclude Wilsons -young with
  tremor
• MRI
• DaT scan
• Research
• SPECT
• PET

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PD - Is it something else ?

• Essential Tremor
• Kinetic /- postural tremor
• 4-12 Hz
• UL, head, voice, LL, trunk, tongue
• gt90 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

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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

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Levo Dopa

• Pros effective
• Cons side effects
• Early side effects NV, ?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

• (DATATOP trial n352 F/U 20 months /- 9)
• Wearing off 50
• Dyskinesias 33
• Severe on-off 10
• Hedonistic homeostatic dysregulation

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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

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Agonists

• 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

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PD whats new

• Genetics
• Drugs
• NSAIDs
• Ibuprofen protective but not other NSIADs
• N136,474
• Stem cells

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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

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Update Multiple Sclerosis
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Update Multiple Sclerosis

• Disease modifying therapies
• CCSVI
• Lifestyle effects
• Sativex
• NMO antibodies

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Update Multiple Sclerosis

• Refresher
• Demyelination
• Inflammation
• Clinically isolated syndrome
• Optic neuritis
• Transverse myelitis
• Brain stem
• motor
• Sensory
• McDonald criteria 2001 2005 2010

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McDonald criteria

• Clinical presentation Additional 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
  MRI or 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
  MRI or Second clinical attack (relapse)
• One attack
• objective clinical evidence of one lesion
• (known as 'clinically isolated
  syndrome') Dissemination in space
  demonstrated by MRI or Up to two MRI
  detected lesions typical of MS plus positive CSF
• AND dissemination in time demonstrated by
  MRI or 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

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Update Multiple Sclerosis

• 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.

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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

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Update Multiple Sclerosis - DMTs

• CCSVI
• Zamboni
• Stem cells
• Lifestyle effects
• Vitamin D
• tobacco
• diet
• NMO antibodies
• Neuromyelitis optica (Devics disease)
• Aquaporin antibodies

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Update Multiple Sclerosis - DMTs

• CCSVI
• Zamboni
• Stem cells
• Lifestyle effects
• Vitamin D
• tobacco
• diet
• NMO antibodies
• Neuromyelitis optica (Devics disease)
• Aquaporin antibodies

• Other neurological antibodies
• MUSK
• VGKC
• NMDA

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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

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Update Stroke

• Risk of stroke after TIA
• Thrombolysis
• PFO

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Update
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Overview

1. Neurology - theres a lot of it about

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Overview

1. Neurology - theres a lot of it about
2. Guidelines, QOFs, and more guidelines

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Overview

1. Neurology - theres a lot of it about
2. Guidelines, QOFs, and more guidelines
3. Do you suffer from Neurophobia ?

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Overview

• Theres a lot of it about
• Guidelines, QOFs, and more guidelines
• Neurophobia widespread

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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

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Guidelines, QOFs, etc..

• NICE PD
• NICE epilepsy
• SIGN epilepsy
• QOF epilepsy
• Stroke and TIA
• Headache
• MS
• And all the others.

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Do you suffer from Neurophobia ?

• A fear of neurosciences and clinical neurology
• Jozefowicz 1994
• Schon Hart et al 2002

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Do you suffer from Neurophobia ?

• A fear of neurosciences and clinical neurology
• Jozefowicz 1994
• Schon Hart et al 2002
• Seeds Sown at medical school ?

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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

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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

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• Our ethos ?
• Referral guidelines ?
• Communication
• Tel [phone]
• Fax [phone]

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Neurology Update

• Paul Hart
• Neurologist
• Epsom St Helier t 0208 296 3355
• f 0208 296 3356
• AMNU _at_ St Georges
• Royal Marsden Hospital