Neurology Update

Paul HartNeurologist

Epsom + St HelierAMNU @ St George’sRoyal Marsden Hospital

Neurology Update Diseases

Parkinsons disease Multiple Sclerosis Epilepsy Stroke Dementia Headache ……..

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 Update Diseases

Parkinsons disease Multiple Sclerosis Epilepsy Stroke Dementia Headache …….. Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III)

associated with hereditary stomatocytosisNeuromuscul 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

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 !?

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

Definition of idiopathic PDDefinition of idiopathic PD

Pathological diagnosisPathological diagnosis

depigmentation + neuronal loss in substantia nigradepigmentation + neuronal loss in substantia nigra

Intraneuronal inclusions- Lewy bodiesIntraneuronal inclusions- Lewy bodies

TTremorremor UL>LLUL>LL AsymmetricAsymmetric Rest tremorRest tremor Tongue lips chinTongue lips chin

RRigidityigidity

AAkinesiakinesia

PPostural instabilityostural instability GaitGait micrographiamicrographia Facial HypomimiaFacial Hypomimia SpeechSpeech

TTremorremor UL>LLUL>LL AsymmetricAsymmetric Rest tremorRest tremor Tongue lips chinTongue lips chin

RRigidityigidity

AAkinesiakinesia

PPostural instabilityostural instability GaitGait micrographiamicrographia Facial HypomimiaFacial Hypomimia SpeechSpeech

Non-motor manifestations Constipation EDS Anosmia REM behaviour disorder Depression Dementia Pain Postural stability Skin Autonomic ….

Clinical Features

SleepSleep 75-90% PD sleep dysfunction75-90% PD sleep dysfunction InsomniaInsomnia Sleep fragmentationSleep fragmentation Sleep akinesiaSleep akinesia NocturiaNocturia Nocturnal panic attacksNocturnal panic attacks RLSRLS Excesssive daytime somnolenceExcesssive daytime somnolence

Drug induced psychosis 10-30%Drug induced psychosis 10-30% reduce parkinson medsreduce parkinson meds monitor responsemonitor response neuroleptic trial quetiapine / clozapine / olanzapineneuroleptic trial quetiapine / clozapine / olanzapine

Mirtazapine RIvastigmine

Neuropsychiatric problemsNeuropsychiatric problems

Depression and DementiaDepression and Dementia

A Clinical DiagnosisA Clinical Diagnosis

Investigations:Investigations: Exclude Wilsons -young with tremorExclude Wilsons -young with tremorMRI MRI DaT scanDaT scanResearchResearch

SPECTSPECTPETPET

PD - Is it something else ? 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 Treatment – what when and how?

1817 James ParkinsonBlood lettingIatrogenic pus formation

2011 DopaminergicNon dopaminergicSymptomaticNeuroprotectiveSurgery – Ablation – DBS – Brain GraftingPreventative

Levo Dopa 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

(DATATOP trial n=352; F/U 20 months +/- 9)

Wearing off50% Dyskinesias 33% Severe on-off 10%

Hedonistic homeostatic dysregulation

Levodopa therapeutic manoeuvresLevodopa 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

AgonistsAgonists

No dyskinesiaNo dyskinesia potentially neuroprotectivepotentially neuroprotective delays use of levodopadelays use of levodopa longer half lifelonger half life no absorption delay/dietary no absorption delay/dietary

effectseffects no metabolic conversionno metabolic conversion

Apomorphine Pergolide Cabergoline Pramipexole Ropinirole Rotigitone

Side effects Ankle oedema Gambling Sexual appetite

PD – whats new

Genetics

Drugs

NSAIDs Ibuprofen protective but not other NSIADs N=136,474

Stem cells

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

PD – whats new - Genetics

Update – Multiple Sclerosis

Update – Multiple Sclerosis

Disease modifying therapies

CCSVI

Lifestyle effects

Sativex

NMO antibodies

Update – Multiple Sclerosis

Refresher Demyelination Inflammation Clinically isolated

syndrome Optic neuritis Transverse myelitis Brain stem motor Sensory

McDonald criteria 2001 2005 2010

McDonald criteriaClinical presentation Additional data needed for MS diagnosis Two or more attacks

objective clinical evidence of two or more lesions None

Two or more attacksobjective clinical evidence of one lesion Dissemination in space shown on MRI

orUp to two MRI detected lesions typical of MS plus positive CSF*orAwait a further relapse suggestive of dissemination in space (ie affecting another part of the body)

One attackobjective clinical evidence of two or more lesions Dissemination in time demonstrated by MRI

orSecond clinical attack (relapse)

One attackobjective clinical evidence of one lesion (known as 'clinically isolated syndrome')

Dissemination in space demonstrated by MRIorUp to two MRI detected lesions typical of MS plus positive CSFAND dissemination in time demonstrated by MRIorDissemination in time demonstrated by MRI (ie new lesion seen on MRI at least 3 months after the original scan)orSecond 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

orAbnormal visual evoked potential plus abnormal MRI AND dissemination in time demonstrated by MRI orContinued progression for one year (determined retrospectively or by

ongoing observation)

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….

Multi-disciplinary care

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 imREBIF sc

1b BETAFERON scFingolimod 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

Update – Multiple Sclerosis - DMTs

CCSVI Zamboni

Stem cells

Lifestyle effects Vitamin D tobacco diet

NMO antibodies Neuromyelitis optica (Devic’s disease) Aquaporin antibodies

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

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

Update – Stroke

Risk of stroke after TIA

Thrombolysis

PFO

Update – ……

Overview

1. Neurology - there’s a lot of it about

Overview

1. Neurology - there’s a lot of it about

2. Guidelines, QOFs, and more guidelines

Overview

1. Neurology - there’s a lot of it about

2. Guidelines, QOFs, and more guidelines

3. Do you suffer from Neurophobia ?

Overview

• There’s a lot of it about

• Guidelines, QOFs, and more guidelines

• Neurophobia widespread

1. 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

2. Guidelines, QOFs, etc…..

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

3. 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 ?

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

Seeds Sown at medical school ?

4. 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

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

Our ethos ?

Referral guidelines ?

Communication Tel 0208 296 3355 Fax 0208 296 3356

Neurology Update

Paul HartNeurologist

Epsom + St Helier t 0208 296 3355f 0208 296 3356

AMNU @ St George’sRoyal Marsden Hospital