An Introduction to Clinical

Neurology
Professor David Corbin
FRCP(Lond), FAAN
 Topics
• Acute Stroke
• Bell’s Palsy
• Epilepsy
• Migraine
• Alzheimer’s Disease
• Parkinson’s Disease
• Tropical Spastic Paraparesis
• Myasthenia Gravis
 Acute Stroke
Sudden vascular event causing loss of
brain function
 Acute Stroke

Ischaemic
Haemorrhage (Cerebral
Infarction)

Intracerebral Subarachnoid Atherosclerosis Embolism to

(ICH) (SAH) involving brain artery Other causes
brain artery
HOW COMMON IS ACUTE STROKE
IN BARBADOS?

First ever (350 / yr) BROS

Recurrent events (500/ yr) BNR
 Stroke incidence rates per 1000 by age
group and gender
25

20
Incidence Rates
/1000 15
Males
10 Females
All cases
5
2001-3
0 BROS
15- 25- 35- 45- 55- 65- 75- >85 Black pop
24 34 44 54 64 74 84
 Proportional frequency (%) of stroke
sub-types
Subtype BROS Range in 10 other
(N=628) studies (N=4578)

Infarction 83.0 (67.3-80.5)

Intracerebral 10.8 (6.5-19.6)

Haemorrhage
Subarachnoid H 2.1 (0.8-7.0)

Undetermined 4.0 (2.0-14.5)

 Role of Brain Imaging in diagnosis of
acute stroke
• To identify haemorrhage
• Possibly identify area of infarction
• MRI for brain stem or lacunar infarction
• Rule out stroke mimics, eg tumour,
subdural haematoma
Hyper-acute
CT scan
Primary
Intracerebral
Haemorrhage
Acute
Subarachnoid
Haemorrhage
on CT brain
 Ischaemic
Stroke
Mechanisms
• Exact cause often
uncertain
• About 20% due to
cardiogenic emboli
• Cardiac investigations
may include ECG,
Holter monitoring,
echocardiogram
 Massive
Cerebral infarct
due to proximal
left middle
cerebral a
occlusion
(MCA)
Left partial
MCA
territory
infarct
Evolution of infarct in R MCA territory
 Reperfusion of the ischaemic
penumbra is critical

Progression over Time (Left to Right)

Infarct Core (Red)……irreversible neuronal damage

Ischemic Penumbra (Green)

TIME IS BRAIN
Acute Left MCA Occlusion:
revascularization after IV thrombolysis < 3HRS

Douen
 Criteria for clot retrieval
Patients who present to major comprehensive stroke
centres may be considered for mechanical thrombectomy
with a stent retriever within 6 hours of onset if :
• prestroke modified Rankin score is 0 to 1
• causative occlusion of the internal carotid artery or
MCA segment 1 (M1) is demonstrated on angiography
• If age ≥18 years
• NIHSS score of ≥6 (ie not a very mild stroke)
• ASPECTS score of ≥6 (there is no extensive infarction)
MERCI RETRIEVAL SYSTEM
 Consider stroke mimics
• Hypoglycaemia
Diabetic oral medication
Insulin
• Seizure
Paralysis on one side may follow
• Migraine
With headache
Bell’s palsy
 Facial Nerve VII
2 types of facial nerve lesion:

• UMN (upper motor neurone, sparing

contralateral occipito-frontalis and orbicularis
oculi)

• LMN (lower motor neurone involving all

ipsilateral facial muscles)
Bell’s palsy is the commonest cause of
LMN VII cranial nerve lesion
Scottish anatomist Charles Bell (1774–1842),
Enquire about:
• loss of taste on same side
• hyperacusis (enhanced sensitivity to noise)
• dryness of eyes or increased lacrimation
(parasympathetic fibres to lacrimal gland and salivary
glands).
Detailed anatomy of CN 7
 Bell’s phenomenon
• Bell’s phenomenon is a sign of weakness of
orbicularis oculi.
• Eyelid closure and eyeball elevation occur together
as a normal phenomenon so that eyeball elevation is
not normally seen.
• Observe the eyeball as the eye closes; if it can be
seen drifting upwards, Bell’s phenomenon is said to
be present.
Bell C. On the motions of the eye, in illustration of the use of the muscles and
nerves of the orbit. Philosophical Transactions of the Royal Society, London1823;
113: 166-186.
 Ramsay Hunt Syndrome
• An interesting cause of facial palsy first described in 1907 by
James Ramsay Hunt
• Due to re-activation of Herpes Zoster virus resident in the
geniculate ganglion with the appearance of vesicles in the
pinna as the virus travels down the sensory neurones
• Hence the pinna should be carefully examined in all cases of
Bell’s palsy, especially if painful.
• Note that activation of the same virus in spinal dorsal root
ganglia causes eruption in spinal dermatomes causing
SHINGLES
SEIZURES AND EPILEPSY
 Definition of Epilepsy and Seizures
Epilepsy (a disease)
 Two or more unprovoked seizures occurring more than 24 hours
apart
 High probability of further seizures after a single unprovoked
event
Seizures (a symptom)
 Paroxysmal change in behaviour due to abnormal neuronal
activity in the brain
 Typically last less than 3 -4 mins (ictal period)
 Status epilepticus: a prolonged seizure
 Many causes, only one of which is epilepsy
 Approx 10% of people worldwide have a single seizure
 Seizures
Seizures (a symptom)
 Paroxysmal change in behaviour due to abnormal neuronal
activity in the brain
 Typically last less than 3 -4 mins (ictal period)
 Status epilepticus: a prolonged seizure
 Many causes, only one of which is epilepsy
 Approx 10% of people worldwide have a single seizure
 ILAE Revision of Seizure Classification
2017

Focal Onset Generalised Onset

• Awareness vs impaired Motor
• Motor manifestations • Tonic / Clonic
• Non-motor • Myoclonic
manifestations • Atonic
• Focal to bilateral tonic- Non-motor
clonic or generalised Sz • Absence (typical or
atypical)
Un-determined
Relative risk for unprovoked seizures after brain injuries

Susan T. Herman Neurology 2002;59:S21-S26

 Age-Specific Incidence of Epilepsy by Gender in
Rochester, Minnesota: 1935-1984

200
Males
Females
Total
Incidence per 100,000

150

100

50

0
0 5 10 15 20 30 40 50 60 70 80

Age (years)
Annegers et al. Epilepsia. 1995;36:327-333.  Hauser
et al. Epilepsia. 1993;34:453-468.
 Status epilepticus
Definitions
• A single seizure lasting > 5 mins
• A series of 2 or more seizures without full
recovery
Presentations
• Convulsive or tonic-clonic status
• Non-convulsive status (absence or CPS)
• Epilepsia partialis continua (partial motor)
 Intractable Epilepsy
• 10-15% of patients fail AED therapy (defined as
medically resistant)
• Definitions of failure (intractability) vary
• Indications for surgical evaluation:
– Adequate management with AEDs for at least 2 years
(maximum tolerated doses)
– Residual seizures sufficiently frequent and severe to
seriously disrupt normal life
• Typically > 1 complex partial seizure per month
Headaches
(Cephalalgia)

Migraine
 International Headache Society
Classification
Primary Headache Secondary or symptomatic
Syndromes headaches
• Migraine • Fever
• Tension type • Head trauma
• Cluster Headaches • Raised ICP
• Others: ice pick, • Temporal Arteritis
exertional, coital, • Sinusitis
thunderclap, cough • Meningitis
• SAH
• Tic douleureux
Migraine pain
Unilateral (but often not)
Anywhere in head
Boring, sharp…….
Described in dramatic terms….
Throbbing, pulsatile, beating...
At least moderately severe….
Aggravated by movement…..
Associated
features
• Nausea
• Vomiting
• Photophobia
• Phonophobia
• Osmophobia
• Any 1 of the above......
 Features of migrainous aura
• Precedes but may coincide with headache
• Visual: fortification spectrum; scintillating
scotoma; teichopsia; blurriness; jumbled up,
distorted images, blindness,...
• Sensory: hemi-body numbness
• Speech (dysphasia)
• Gradual onset; less than 60 mins
• Typically headache follows but may be absent
Depiction of migrainous aura with fortification
spectra and scintillating scotoma (teichopsia)
Depiction of migrainous aura with fortification
spectra
Visual
Distortion in
Migrainous
aura
The Stages of a Migraine attack
Spreading oligaemia by xenon 133 PET scanning in a
patient experiencing an aura. Lauritzen and Olesen, 1984
Olesen et al.
 Management of Migraine
Education about major
dietary triggers
Chocolate
Cheese
Alcohol
Nuts
Hot Dogs
Pepperoni
Mono-sodium glutamate
Avocado pears
 Management of Migraine
• Headache diary
• Frequency
• Female hormones
• Menstrual pattern
• Weekend headache
• First week of holiday
• Dietary check
 Management of Migraine
General points
• Start analgesia early
• Gastric absorption is inhibited
• Hence combination of analgesia and
antiemetic
• Some analgesics make nausea worse
• Caffeine often added to aid absorption
• When headache is at peak, analgesia is less
effective
• A sedative to induce sleep may be useful
The Trigemino-vascular system
 Cluster Headaches vs Migraine
Cluster Headaches
• <0.1% prevalence
• M>F 3:1; young adults
• Retro-orbital pain
• Onset at night
• Paces up & down
• 1-3 attacks /day/ 8-10 wks
• Attack 30 to 180 mins
• Recurs on consecutive yrs
• Ipsilateral ptosis / redness /
lacrimation (autonomic
dysfunction)
Migraine
• 16%
• M<F 1:2; age spectrum
• Site of pain more variable
• Onset random
• Prefer dark room / to be still
• Attack 2 hrs to 72 hrs
• No autonomic features
• Prodrome and / or aura in
some
 Tension-type headaches
(Episodic and chronic)
• No added features other than headache
• Headache usually mild to moderate
• Mostly episodic and relieved by simple
analgesics
• Occasionally chronic and disabling as a chronic
pain syndrome (disordered pain processing)
• Amitriptylene of proven value
Tension-type headache: distribution
 Analgesic Rebound Headaches
• Common cause of persistent daily headache
• Any analgesia taken for more than 2-3 days
per week
• Background of migraine or tension type
headache or post-traumatic headache
• Analgesics must be withdrawn
• May be replaced by amitriptylene
DEMENTIA
 Dementia in general
• Chronic global loss of cognitive function
from previously higher level
• A state of cognitive loss that is not transient
• Loss of function in multiple domains, eg
aphasia is not dementia
• Loss of memory alone is Amnesia
 Causes of dementia
• Alzheimer’s Disease
• Multiple cerebral infarction (Vascular Dementia)
• Mixture 1 and 2 (may be most common of all)
• Fronto-temporal dementias eg. Lewy body disease,
progressive supranuclear palsy, multisystem atrophy,
cortico-basal degeneration
• Huntington's disease
• Creutzfeld-Jacob Disease, post-cranial radiation,
post-encephalitis
German psychologist
and neuropathologist

Described first
case in 1907
of a female, age 51
memory loss,
paranoia, and
partial loss of
language function
 Loss of cognitive function in the area
of:
• Language (aphasia)
• Abstract thinking, organizational ability (executive
function)
• Visual processing: geographic, recognition (agnosia)
• Skilled motor activities in the absence of sensory loss
or motor weakness (apraxia)
• Most pts are unaware of their cognitive deficits
(anosognosia)
Typical course of AD
 Deficits in Spatial Ability and
Orientation
• Getting lost in familiar places
• Difficulties in dressing (dressing apraxia)
• Difficulties in object recognition (agnosia)
• Difficulties in person recognition
(prosopagnosia)
 Deficits in Reasoning or Handling
Complex Tasks
• Loss of interest or inability to perform hobbies
or chores
• Use of telephone
• Loss of ability to deal with finances, cheque
book, tax forms, bills, shopping, meal
preparation
• Housekeeping
• Driving: accidents, getting lost
• Impairment of occupational activities
 Behavioural disturbances in AD
(10 -70%)
• Delusions
• Hallucinations
• Agitation and aggression
• Depression
• Anxiety
• Elation and euphoria
Behavioural disturbances in AD (2)
• Apathy and indifference
• Disinhibition
• Irritability and lability
• Sleep disorders
• Appetite and eating disorders
 Late features in AD
• 10% seizures
• Motor (pyramidal) tract signs
• Sphincter involvement (incontinence)
• Extrapyramidal tract signs
• Bedridden in fetal position (regression)
• Late clinical events in progressive dementia
are similar regardless of the cause
 AD vs Vascular Dementia
• Gradual • Relatively acute
• Slowly progressive • Stepwise
• No signs • Focal signs
• Early loss of memory • Not as prominent
• Loss of executive • Often severe
function a late feature • Evidence of vascular
• Normal or atrophic injury on scan
brain scan
 Pathology of Alzheimer’s Disease

Senile plaques with amyloid protein at the core

Alzheimer’s disease: cerebral cortical pathology

Neurofibrillary tangle replacing the cytoplasm

The spread of NFT correlates with worsening
symptoms in AD
 Risk Factors for AD
• Age
• Female gender
• Positive family history
• Apolipoprotein genotype
• Low educational attainment
• Multiple head injuries
• Down’s syndrome
• Vascular disease
 Incidence of AD: women > men
• According to the Framingham (USA) study, a non-
demented 65 yr old man has a 6.3 % chance of AD
compared to 12% for women.

• In the Kungsholmen Project, Stockholm (Sweden)

age-adjusted odds ratio for women was 3.1 for AD
 Genetics of AD
• First degree relatives have a 38% risk of AD
by age 85
• Genetic factors account for 40% of pop risk
– Familial aggregation
– Autosomal dom (10%)
PARKINSON’S DISEASE
 Parkinson’s Disease (PD)
After Alzheimer’s disease, PD is the second most common
degenerative disease of the brain

First described by James Parkinson 1817

….Involuntary tremulous motion / with lessened muscle power in
parts not in action/ and even when supported with a propensity
to bend the trunk forward/ and to pass from a walking to a
running pace/ the sense and intellects being uninjured ………(the
latter since proven not to be true)

Jean Martin-Charcot 1871 “Maladie de Parkinson”

….Considerable time lapse between the thought and the action
 Clinical features of PD
MOTOR NON-Motor
 Bradykinesia  Anosmia
 Resting tremor (4-6Hz)  Constipation
 Rigidity
 Depression
 Postural instability
 Micrographia
 Sleep disturbance
 Masked face  Bladder dysfunction
 Stooped, shuffling gait  Cognitive loss
 Decreased arm swing
when walking
What part of the brain is affected?
 Non-motor aspects of PD
Anosmia
• Gradual loss of smell and impairment of taste
affects 90%
• Degeneration of the anterior olfactory nucleus
and olfactory bulb
• One of the earliest features of PD
• May precede the motor signs and symptoms
and therefore can be useful in helping to
identify persons at risk of PD
 Non-motor aspects of PD
Depression
• Fifty percent of patients
• Any phase but may precede motor symptoms in
30%
• Difficult to diagnose / features overlap with PD
• Viewed as an intrinsic part of the PD not simply a
“reaction”
• Prominent apathy and anxiety
• Depression accelerates the cognitive decline
• Interferes with sleep
 Non-motor aspects of PD
Sleep disruption
• Daytime somnolence
• Insomnia occurs in 60 to 80% of patients.
• Difficulty falling asleep or staying a sleep.
• Rigidity frequently causes difficulty turning in
bed.
• Medications can also cause insomnia.
• Bladder dysfunction often disturbs sleep
• Features may pre-date diagnosis
 Non-motor aspects of PD
Dementia
• Cognitive dysfunction (mild, moderate, or
severe) eventually develops in about 70%
• Mainly in later stages and > 65 years
• Often frontal lobe dysfunction, eg.
• difficulties with complex tasks, long-term
planning
• memorizing or retrieving new information
• poor attention
• word fluency
 Non-motor aspects of PD
Autonomic dysfunction
• Constipation occurs in over 75%.
• Bladder dysfunction occurs in over 50%.
• Orthostatic hypotension is seen in 30-58%
(usually without symptoms such as dizziness)
• Excessive sweating
• May predate the diagnosis.
 What happens in the brain in PD?
Progressive loss of dopaminergic neurones in the
substantia nigra. Approx 70% have died before
symptoms appear.

Microscopically
Clumps of abnormal
protein appear as the
affected neurones die
(Lewy Bodies)
Quantity of dopamine projections to striatum can
be estimated during life

Measures the density of dopamine receptors by tagging using a

special radiopharmaceutical agent and SPECT scanning…..the
brighter images indicate more surviving neurones in the basal
ganglia. PD=Parkinson Disease. [PET scanning]
 Epidemiology of PD
• Average incidence is 20 per 100,000 in UK
• Average age of onset 62.5 years
• Prevalence increases with age
• 4% cases less than age 50
• Prevalence in UK :
60-65 342 per 100,000 / 1%
>80 1265 per 100,000 / 4%
• Men 1.5 times more affected than women
• In USA , African-Americans and Asians less likely
than Caucasians to develop Parkinson’s
 MPTP (designer opiate)
The case of the frozen addicts*
• 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Lipophilic
• Converted to MPP+ by MAO-B / DA transport
• Kills DA-producing neurons / complex 1 toxic
• Instant Parkinsonism
• MPP+ compounds used in herbicides
• Retenone commercial SN toxin

William Langston 1995

 What causes PD?
• Unknown
• MPTP
• Heavy metals (Iron and Manganese)
• Pesticides/Herbicides (Rotenone, paraquat, etc)
• Rural Living/Agricultural workers studies not
convincing
• Possibly gene / environment interaction
• Cigarette smoking/Coffee drinking protective!
 Loss of independence due to PD

• Community-based Norwegian study

• 189 PD vs 174 age-sex controls
• 16% vs 6% loss at diagnosis
• At 5 years 41% of PD lost independence vs 9%
controls

Bjornestad A, et al. Neurology 2016

WELL-KNOWN PERSONS WITH PD
Mohammed Ali lighting the Olympic
cauldron in Atlanta 1996

Retired 1981

Diagnosed1984 (age 42)

Repeated head trauma or

PD.
Brian Grant

• Six foot 9 inches Basketballer

• Diagnosed age 37
• 3 years post retirement
• Active foundation
Michael Fox

• Most famous for his role as Marty McFly in the

Back to the Future movies
• Diagnosed with young-onset Parkinson’s
disease in 1991 at the age of 30.
• He eventually established the Michael J. Fox
Foundation, which raises money for research.
 Other well-known PD sufferers
• Johnny Cash 1932-2003
• Maurice White 1941-2016
• Charles Schutz 1922-2000
• Pope John Paul II 1920 - 2005
• Billy Graham Nov 1918– Feb 2018
• Janet Reno 1938-2016
• Billy Connolly b.1942
Peripheral Neurology
 Patterns of motor weakness
• Hemiparesis / plegia
• Quadriparesis /-plegia
• Paraparesis / -plegia
• Monoparesis
• Proximal muscle weakness
• Distal weakness / single nerve or many nerves
• Facial
• Bulbar
 Common patterns of sensory loss
• Hemi-body (A) • Brown-Sequard
• Crossed Syndrome (F)
hemianaesthesia (B) • Sacral sparing
• Sensory level (C) • Saddle anaesthesia
• Suspended or • Dermatomal (G)
segmental (D) • Peripheral Nerve (H)
• Glove and stocking (E) • Trigeminal

*A-H : see next slide

Subacute Quadriparesis

GB female
Age 81
Spastic paraparesis

Structural causes
Benign or malignant
HTLV-I associated Myelopathy

Previously known as Jamaican

Neuropathy or Tropical Spastic
Paraparesis
 MR imaging and pathologic specimen showing thoracic
spinal cord atrophy from patients with HAM/TSP.

©2009 by BMJ Publishing Group Ltd Cooper S A et al. Pract Neurol 2009;9:16-26
 Spread of HTLV-I from Africa
• Africa only continent where all HTLV-I (human T-cell
lymphotropic virus type I) and all STLV (simian
equivalent) sub-classes are found
• Simian-human transmission suspected
• Spread to Japan, Melanesia, Native American (north and
south) and Australian aboriginies prior to trans-atlantic
slave trade
• Type A predominates. Other subtypes; B, D, F, E in Africa,
C in Melanesia.
• Cause of endemic myelopathy (spastic paraparesis) and
adult T-cell leukaemia in the Caribbean
Hypotheses for the spread of HTLV-I
 Presence of ancient HTLV-I provirus DNA in an
Andean mummy

 Andeans similar to Japanese genetically.

 Similar HTLV-I seroprevalence.
 Nucleotide sequences of ancient HTLV-I-pX and HTLV-I-
LTR clones isolated from mummy bone marrow were
similar to those in contemporary Andeans and Japanese
 HTLV-I was carried with ancient Mongoloids to the Andes
before the Colonial era.

Nature Medicine December 1999

Volume 5 Number 12 pp 1428 - 1432
VARIABLE WEAKNESS
 Myasthenia Gravis
• My….Asthenia
• Variable
• Fatiguability
• Eyes: diplopia / ptosis
• Chewing
• Swallowing
• Limbs (proximal > distal)
• Respiratory
 Diagnosis of MG
• IV edrophonium (tensilon
test)

• Repetitive stimulation at 3
Hz: decrement in muscle
action potential (MAP)
amplitude and area

[EMG machine]
Golden Retriever
with MG
40 secs post
edrophonium
Neuromuscular
Junction
(Antibody Tests)

TARGETS
A: Antiacetyl choline
receptor (AchR)
B: Muscle specific
kinase (MuSK)
C: Lipoprotein
receptor-related
peptide 4 (LRP4)
D: Other (congenital)
 Thymus in MG
a) About 15% of Patients
with MG have a thymoma
b)CT thorax imp test
Lymphoid gland
important for T cell
function
c) Removal of gland may
1) Prevent malignancy
2) Improve chances of
better outcome
Subgroups of patients with MG

Gilhus NE. N Engl J Med 2016;375:2570-

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