Vague Neurological Disorders Dr. Philip Smalley MD FRCPC SVP & Global Chief Medical Officer RGA International Rose Conference, September 17, 2015
Agenda Vague neurological symptoms associated with: Alzheimer s, Parkinson s, Stroke, Traumatic Brain Injury, Multiple Sclerosis and Migraine Headaches New definition of TIAs and its implication on the diagnosis and incidence of stroke Usual time course for recovery to assess degree of disability How to evidence these findings?
Causes of Long Term Disability Claims - 2013 Impairment New Claims Existing Claims MSK 28.6% 28.7% Nervous System 7.7% 15.2% Circulatory / CVD 8.7% 12.4% Cancer 15.1% 9.1% Mental 8.3% 7.7% Council for Disability Awareness (CDA) 2014 Report
Critical Illness Impairments Demanding Neurological Sequelae Stroke Multiple Sclerosis Coma Major Head Trauma Benign Brain Tumor Parkinson s Disease Alzheimer s Disease Bacterial Meningitis Encephalitis Motor Neuron Disease Muscular Dystrophy Blindness Deafness Paralysis Loss of speech Loss of Independence
Alzheimer s Disease Incidence Rates Doubles every 6.3 years after age 60 World Alzheimer Report 2015 Brookmeyer R et al. Alzheimers Dement. 2011;7(1):61-73
Risk Factors for Alzheimer Disease Diabetes Hypertension Obesity Depression Physical Inactivity Smoking Low education Barnes, D et al, Lancet Neurology July 19, 2011 6
Role of Our Microbiome 10X more bacteria than human cells Health and disease Obesity, Metabolic syndrome, Diabetes, Autoimmune-disease Anxiety, neuropsychiatric diseases, schizophrenia and Alzheimer Disease Hill JM et al, Front Aging Neurosci. 2014 Jun 16;6:127
Caregivers of Demented Relatives have more disability Ho, A., Collins, S., Davis, K. & Doty, M. A Look at Working-Age Caregivers Roles, Health Concerns, and Need for Support (2005)
Old Definition Questionnaires Neuropsych testing Alzheimer s Disease New Definition Biomarkers CSF exam PET scan IMPACT Make diagnosis 10 years sooner Sperling RA et al, Alzheimers Dement. 2011 May;7(3):280-92
Pathology of Parkinson s Disease (PD) Destruction of the Substantia Nigra in mid-brain
Non-motor Symptoms PD Diminished sense of smell (90% of PD) Sleep disturbance / REM Behaviour Disorder 38% develop Parkinson s Low voice volume Painful foot cramps Fatigue / Daytime sleepiness Falls Autonomic dysfunction: Constipation, Drooling, Increased sweating, Urinary frequency/urgency Male erectile dysfunction
Motor Symptoms - PD Tremor (85%) (resting, 4-6 Hz, spares head) Bradykinesia Rigidity and freezing in place Stooped, shuffling gait Decreased arm swing when walking Difficulty arising from a chair Micrographia (small handwriting) Lack of facial expression Slowed activities of daily living Difficulty turning in bed Postural instability
Mental Manifestations of PD 40-50% of PD patients get depression 50% get psychotic symptoms 20-40% get dementia If occurs < 1 year of motor PD features, then likely diagnosis is Lewy Body Disease, not PD Less common if PD onset is less than 50
Hoehn and Yahr Staging Scale Stage 1 One side, mild, not disabling Stage 2 Bilateral, minimal disability, posture and gait affected Stage 3 Significant slowing of movement, early balance problems walking and standing Stage 4 Severe symptoms, can still walk to limited extent, unable to live alone Stage 5 Invalidism complete, cannot stand or walk Hoehn, MM, Yahr, MD, Neurology 1967; 17:427
Time Spent in Each Stage Mean duration of disease 14.6 years Time spent in each stage: Diagnosis 1.5 years Maintenance 6 years Complex 5 years Palliative 2.2 years MacMahon DG et al, J Neurol. 1998 May;245 Suppl 1:S19-22
Deep Brain Stimulation Surgical pacemaker inserted in brain Improves disability in some PD patients $15,000 - $20,000
Stroke: Signs and Symptoms Depend on Location Left
Clinical Presentation Abrupt onset of focal neurological signs Deficit may remain fixed or rapidly improve or progress 10% of strokes have preceding history of one or more Transient Ischemic Attack (TIA) Seizures at the time of stroke occur in 3-5% of infarctions Headache is not common with simple stroke 18
Differential Diagnosis Transient Ischemic Attack Lasts usually 5 20 minutes Others. Seizure Hypoglycemia Migraine Multiple Sclerosis Cranial or peripheral nerve palsy Subdural hematoma
Migraine Headache ± Aura 12% of population, Female > Male, highest in 25 45 age group 19th leading reason of disability worldwide as per WHO Number of neurologic and psychiatric disorders, including epilepsy, stroke, major depression and anxiety disorder, show increased co-morbidity with migraine Headache 4-72 hours Unilateral and throbbing o 75%: Headache and no Aura o 38%: Aura with headache o 4%: Aura and no headache Aura Visual disturbances
Transient Ischemic Attack (TIA) Old Definition New Definition IMPACT Time based Definition < 24 hours Imaging based Definition 30% - 50% of TIAs actually have a related deficit TIA 28% STROKE 8.1% Easton JD et al, Stroke. 2009 Jun;40(6):2276-93
Prevalence Silent Brain Infarcts Silent strokes are common and >> symptomatic strokes Vermeer SE et al. Stroke. 2002 Jan;33(1):21-5
Stroke Prognosis At 5 years post Stroke: 71% had mild impairment (NIHSS < 5) 22.5% had dementia 33% had depression, falls or incontinence 9.4% developed seizures 15% institutionalized At 6 months post Stroke, 6% - 16% have completely recovered with Rankin Score 0 (Bruins Slot, K et al. BMJ 2008;336;376-379) Feigin VL et al, Neurology. 2010 Nov 2;75(18):1597-607
Modified Rankin Score Score 0 = No symptoms Score 1 = No significant disability despite symptoms, able to carry out all usual duties and activities Score 2 = Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance Score 3 = Moderate disability, requiring some help, but able to walk without assistance Score 4 = Moderately severe disabililty, unable to walk without assistance and unable to attend to own bodily needs without assistance Score 5 = Severe disability, bedridden, incontinent and requiring constant nursing care and attention Score 6 = Dead
Stroke Recovery Course 58% of strokes reach maximum recovery by 2 weeks Neurological recover plateau s 12 weeks after a stroke Newman M. Stroke. 1972 Nov-Dec;3(6):702-10
Traumatic Brain Injury Coup / Contrecoup Injury Ropper, Allan H et al. N Engl J Med Volume 356(2):166-172 January 11, 20
Traumatic Brain Injury (TBI) Sequela Post-concussion Syndrome Memory difficulty has ranged from 4% to 59% Concussion does not cause a loss of autobiographical information, such as one s name and birth date Headache and dizziness have been as high as 90% at 1 month and approximately 25% at 1 year or more 32% of mild TBI patients have severe fatigue 6 months post TBI Focal neurological signs Seizures (20% if intracranial bleed and can be recurrent) Ropper, AH et al. N Engl J Med 2007;356(2):166-172 Stulemeijer M et al, J Neurol. 2006 Aug;253(8):1041-7
Anosmia (Loss of Smell) Occurs in 11% - 33% of TBI But 1% - 2% of population have some olfactory dysfunction Test on exam or with Evoked Response Olfactometry MRI and SPECT can be abnormal Recovery 11.3% - 23.3% return to normal < 6 months and unlikely to return to normal > 6 months Some recovery for up to 2 years
Multiple Sclerosis (MS) Slowly progressive autoimmune disease targeting myelin in the CNS First described 1868
Symptoms - MS Most common presenting symptoms are: Paresthesias (tend to resolve in 6 8 weeks) Weakness or fatiguibility Visual disturbances Bladder or sexual dysfunction Excess heat may worsen symptoms Uhthoff phenomenon
Signs / Examination - MS Scotoma, decreased acuity, colour blindness, diplopia Limb weakness but testing often does not correlate with degree of difficulty walking Ataxia, dysarthria, tremor, slow scanning speech
Mental Manifestations - MS Fatigue Seen in 72% of patients Responsible for 65% of the disability Not correlated to degree of physical disability Might respond to brief naps Apathy, lack of judgment, emotional lability, euphoria, sudden crying or forced laughter Dementia can be late symptom Depression and suicide
Relapses - MS Symptoms develop over days, peak less than a week, remain constant for 3 to 4 weeks, slowly resolve over ~ 1 month Relapses every ~1-2 years but ~5-10 new lesions per year on MRI Frequency of relapses decreases with age & duration of disease Most recovery occurs in first 3 months but can take up to a year
Types of MS Relapsing Remitting 85-90% start with RRMS More inflammatory Benign 10% of MS is benign Secondary Progressive 50% of RRMS develop Secondary Progressive MS More neurodegenerative Primary Progressive Primary Progressive MS Lack of response to immunetx
Kurtzke Expanded Disability Status Scale (EDSS) 0 = Normal exam 1 = No significant disability despite symptoms, able to perform all duties/activities 2 = Slight disability, unable to carry out all previous activities, able to look after self 3 = Moderate disability, fully ambulatory 4 = Fully ambulatory, self-sufficient, can walk 500 m without aid or rest 5 = Disability severe enough to impair full daily activities 6 = Uses cane or crutch 7 = Restricted to wheelchair 8 = Restricted to bed or chair 9 = Can still communicate and eat
Major Causes of Disability in MS Fatigue Cognitive and memory Spastic paraparesis Poor coordination Sphincter dysfunction
Median time to Disability - MS To EDSS 3 was 8-12 years To EDSS 6 was 14-28 years Time to EDSS 3 for progressive disease: Secondary progressive: 8 years Primary progressive: 3 years Pittock SJ et al, Neurology 2004;62:601-6 Degenhardt A et al. Nat Rev Neurol. 2009;5(12):672-82
Summary Ageing work force and adverse lifestyles leading to more neurological disability claims New clinical TIA definition Neurological recovery unlikely after 3 months Vague neurological symptoms are common and can be disabling psmalley@rgare.com
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