Cognitive Impairment and Dementia an Update FRONTIERS in NEUROLOGY
Neurology Update
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Transcript of Neurology Update
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