Transcript Neurology Update - epsomgpstudyday

Neurology Update
Paul Hart
Neurologist
Epsom
+ St Helier
AMNU @ St George’s
Royal Marsden Hospital
Neurology Update
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Diseases
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Parkinsons disease
Multiple Sclerosis
Epilepsy
Stroke
Dementia
Headache
……..
Neurology Update
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Diseases
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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 Update
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Diseases
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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
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Neurology Top 10 Tips
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Services
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TWRs
Direct access investigations
Local provision
How to get the most out of your neurologist
Update - Parkinsons disease
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Suspected PD
Unsuspected PD – making the penny drop
PD review
Common
Increasing prevalence
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Predicted to treble over the next 50 years
Age 50 – 10:100,000
Age 80 – 200:100,000
< 80% confirmed at post-mortem !?
Classification of Movement Disorders
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Akinetic
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Idiopathic Parkinsons
Disease
Parkinsons plus
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MSA
PSP
DLB
CBD
Secondary Parkinsonism
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Hyperkinetic
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Chorea
Ballism
Tremors
Myoclonus
Wilsons disease
Dystonia
Tics + Tourettes
Sleep related movement
disorders
Ataxia
Dyskinesias
Psychogenic
Definition of idiopathic PD
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Pathological diagnosis
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depigmentation + neuronal loss in substantia nigra
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Intraneuronal inclusions- Lewy bodies
Clinical Features
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Tremor
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UL>LL
Asymmetric
Rest tremor
Tongue lips chin
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Non-motor manifestations
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Rigidity
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Akinesia
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Postural instability
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Gait
micrographia
Facial Hypomimia
Speech
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Constipation
EDS
Anosmia
REM behaviour disorder
Depression
Dementia
Pain
Postural stability
Skin
Autonomic
….
Sleep
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75-90% PD sleep dysfunction
Insomnia
Sleep fragmentation
Sleep akinesia
Nocturia
Nocturnal panic attacks
RLS
Excesssive daytime somnolence
Neuropsychiatric problems
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Drug induced psychosis 10-30%
reduce parkinson meds
monitor response
neuroleptic trial quetiapine / clozapine / olanzapine
Depression and Dementia
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Mirtazapine
RIvastigmine
A Clinical Diagnosis
Investigations:
Exclude Wilsons -young with tremor
MRI
DaT scan
Research
SPECT
PET
PD - Is it something else ?
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Essential Tremor
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Kinetic +/- postural tremor
4-12 Hz
UL, head, voice, LL, trunk, tongue
>90% undiagnosed
73% report significant disability
Treatment: medical, botox, surgical
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Drug induced Parkinsonism
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12% of 328 patients referred to
secondary care
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Parkinsons plus
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MSA
PSP
LBD
CBD
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Prochloperazine 32%
Typical antipsychotics 42%
atypical antipsychotics 18%
Metoclopramide 11%
Amiodarone 8%
Lithium 8%
Antihistamines 8%
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Promethazine and
cinnarazine
Valproate 5%
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
Levo Dopa
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Pros: effective
Cons:side effects
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Early side effects – N+V, HR, BP
Late SE
motor fluctuations
dyskinesias
neuropsychiatric
(DATATOP trial n=352; F/U 20 months +/- 9)
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Wearing off 50%
Dyskinesias 33%
Severe on-off 10%
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Hedonistic homeostatic dysregulation
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Symptoms unresponsive to L-Dopa
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postural instability
freezing phenomena
speech
sialorrhoea
depression and dementia
ANS - sweating, urinary frequency, constipation
sensory symptoms + pain
Tremor
REM sleep behaviour disorder
Levodopa therapeutic manoeuvres
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On with dyskinesia vs Off without dyskinesia
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CR preparations
Hyperfractionate dosing schedule
COMT inhibitors - entacapone, tolcapone
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Stalevo
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Levodopa carbidopa entacapone
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50 / 12.5 / 200
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Stalevo “50” “75” “100” “125” “150” “200”
MAO inhibitors - selegeline, rasagiline
Amantadine
Dopamine Agonists
Duo-dopa
Apomorphine pump
Agonists
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No dyskinesia
potentially neuroprotective
delays use of levodopa
longer half life
no absorption delay/dietary
effects
no metabolic conversion
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Apomorphine
Pergolide
Cabergoline
Pramipexole
Ropinirole
Rotigitone
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Side effects
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Ankle oedema
Gambling
Sexual appetite
PD – whats new
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Genetics
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Drugs
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NSAIDs
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Ibuprofen protective but not other NSIADs
N=136,474
Stem cells
PD – whats new - Genetics
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15% PD patients have an affected 1st degree relative
5% due to mutation in one of several specific genes
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In most cases, people with these mutations will develop PD.
All rare except LRRK2
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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.
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10% familial PD
3% sporadic PD
Genome wide association studies
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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
Mutations in GBA are known to cause Gaucher's disease
All identified risks account for 2.5-3x risk
Update – Multiple Sclerosis
Update – Multiple Sclerosis
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Disease modifying therapies
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CCSVI
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Lifestyle effects
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Sativex
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NMO antibodies
Update – Multiple Sclerosis
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Refresher
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Demyelination
Inflammation
Clinically isolated
syndrome
 Optic neuritis
 Transverse myelitis
 Brain stem
 motor
 Sensory
McDonald criteria 2001
2005 2010
McDonald criteria
Clinical presentation
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Two or more attacks
objective clinical evidence of two or more lesions
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Two or more attacks
objective clinical evidence of one lesion
One attack
objective clinical evidence of two or more lesions
Additional data needed for MS diagnosis
None
Dissemination in space shown on MRI
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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)
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
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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)
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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)
Update – Multiple Sclerosis
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Treatment of MS
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Relapses
 Treatment
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Prevention
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DMTs
Treatment of symptoms
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Oral methyprednisilone 500mg od - 5days
Fatigue
 Amantadine
 Modafinil
Depression
Spasticity
 Baclofen
 Tizanidine
 Sativex
Bladder
Etc….
Multi-disciplinary care
Update – Multiple Sclerosis - DMTs
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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.
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Beta interferon
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1a
1b
AVONEX
REBIF
BETAFERON
im
sc
sc
po
COPAXONE
sc
Fingolimod
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Glatiramer acetate
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Natalizumab TYSABRI
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Different mechanism, similar effect
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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Cardiac toxicity
Update – Multiple Sclerosis - DMTs
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CCSVI
 Zamboni
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Stem cells
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Lifestyle effects
 Vitamin D
 tobacco
 diet
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NMO antibodies
 Neuromyelitis optica (Devic’s disease)
 Aquaporin antibodies
Update – Multiple Sclerosis - DMTs
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CCSVI
 Zamboni
Other neurological antibodies
•MUSK
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Stem cells
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Lifestyle effects
 Vitamin D
 tobacco
 diet
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NMO antibodies
 Neuromyelitis optica (Devic’s disease)
 Aquaporin antibodies
•VGKC
•NMDA
Update – Epilepsy
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More New AEDs
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Enhance slow activation of Na channels
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Ca channel lockers + carbonic anhydrase inhibitor
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Lacosamide
Rufinamide
Zonisamide
Sudden unexplained death in epilepsy
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Epilepsy SMR 1.6-9.3
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Underlying disorder / status / accidents / suicide / Rx related death / SUDEP
8-17% of deaths
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Memory
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Psychosocial
Update – Stroke
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Risk of stroke after TIA
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Thrombolysis
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PFO
Update – ……
Overview
1.
Neurology - there’s a lot of it about
Overview
1.
2.
Neurology - there’s a lot of it about
Guidelines, QOFs, and more guidelines
Overview
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2.
3.
Neurology - there’s a lot of it about
Guidelines, QOFs, and more guidelines
Do you suffer from Neurophobia ?
Overview
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There’s a lot of it about
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Guidelines, QOFs, and more guidelines
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Neurophobia widespread
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Neurological disorders are common
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WHO
“Neurological disorders – a public health challenge”
“one of the greatest threats to public health”
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Mortality vs DALYs
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Neurological disease accounts for 20% of admissions to general
hospitals
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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
3.
Do you suffer from Neurophobia ?
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A fear of neurosciences and clinical neurology
 Jozefowicz 1994
 Schon Hart et al 2002
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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
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52 clinics per month
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94% of ward referrals seen on day of referral, 99% within 48 hrs
Neurology – top ten tips
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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 ?
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Referral guidelines ?
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Communication
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Tel 0208 296 3355
Fax 0208 296 3356
Neurology Update
Paul Hart
Neurologist
Epsom
AMNU
+ St Helier
@ St George’s
Royal Marsden Hospital
t 0208 296 3355
f 0208 296 3356