Transcript Document 262596

Common neurological
conditions and their risk factors
Clinical Sessions 2011 – Masaryk University
Vanda S. Couto Reis
Most common neurological conditions
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Headache
Dementias
Epilepsy
Movement disorders
Cerebellar
dysfunction
Cranial nerve lesions
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Myelopathies
Motor neuron
diseases
Radiculopathies and
plexopathies
Disorders of NMJ
Vascular disorders of
nervous system
DEMENTIA
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Definition – congenital or acquired
syndrome associated with lobal
deterioration of intellect, behaviour and
personality
Progressive, usually with diffuse
involvement of both cerebral hemispheres
Usually no alteration of the level of
consciousness
IMPAIRMENT OF MEMORY!!!
General clinical features
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Loss of memory for recent events
Abnormal behaviour
Intellect/ mood changes
Difficulties coping with ordinary tasks
Disorientation in time, place and person
Double incontinence
Psyquiatric features (paranoia)
Rate of progression dependent on the
cause
History and examination
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Obtain history from patient + confirm
with friend / family
Neurological examination:
Focal signs
Involuntary movements
Pseudobulbar signs
Primitive reflexes (pout, grasp,
palmomental)
Gait disorders
Investigations
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Blood tests – exclude hypothyroidism, vit B9 and
B12 deficiency, syphilis
Cranial imaging – CT, MRI to exclude space
occupying lesions, normal pressure
hydrocephalus, etc
EEG – periodic complexes may indicate Prion’s
disease
Muscle biopsy – mitochondrial cytopathies
Genetic testing – Huntington mutation, APP,
apolipoprotein E4 mutations, prion protein gene
mutation
Brain biopsy – only when treatable cause of
dementia suspected but not diagnosable by any
other means (cerebral vasculitis)
Differential diagnosis
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Primary neurodegenerative – Alzheimer’s, Pick’s,
Huntington’s, Lewy body’s disease
Metabolic – hypothyroidism, vit B12 or B9
deficiency, mitochondrial cytopathies, Wilson’s
disease
Infections – HIV, CJD+CJDv, syphilis
Vasculitis and other inflammatory diseases
Normal pressure hydrocephalus
Space-occupying lesion – chronic subdural
hematoma
Pseudodementia – severely depressed patients
Alzheimer’s disease
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Most common cause of dementia
Early onset – chrom 21 associated
with gene for APP
Late onset – chrom 19 associated
with gene for apolipoprotein E4
Mutations in genes presenilin 1 and
2
Particularly high incidence among
Down syndrome patients!!!
Pathology
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Senile plaques and neurofibrillary
tangles in brain
Senile plaques = dystrophic
neurites clustered around a core of
B amyloid protein derived from APP
Neurofibrillary tangles = from
microtubule-associated protein tau
Majority in temporal and parietal
lobes
Clinical features
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Progressive dementia evolving over many
years
Results in:
Aphasia
Geographical apraxia
Early and severe loss of short term
memory
Seizures (uncommon) in advanced stages
Pyramidal and extrapyramidal features
Diagnosis
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Definite diagnosis – only from
pathological findings (progressive
dementia + negative routine tests)
CT – non-specific cerebral atrophy
with enlarged ventricles
MRI – volumetric analysis of
temporal lobes
Drug treatment
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Acetylcholinesterase inhibitors – tacrine,
galantamine, rivastigmine, donepezil
Arrest symptoms for +/- 6m but do not
alter the course of the disease
Combine with memantine to improve
symptoms in advanced stages
Current research – inhibit
hyperphosphorylation of protein tau
EPILEPSY
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Definition: abnormal, sudden, excessive
and rapid electrical discharges arising
from cerebral neurons (usually selfterminating with tendency to recur)
3-5% of population – 1 seizure in life
0.5% of population – recurrent seizures,
90% of which well controlled by
pharmacotherapy and characterised by
proloned remissions
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Seizure – intermittent, stereotyped
disturbance of consciousness, behaviour,
emotion, motor function or sensation
arising from abnormal neuronal firing
Status epilepticus – state of continued/
recurrent seizures with failure to regain
consciousness between episodes (medical
emergency)
Prodrome – premonitory changes in
mood/ behaviour that precede attack by
hours
Aura- subjective sensation that precede
and mark the onset of the seizure and
may help localizing the seizure origin
Aetiology
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50% of cases – no apparent cause
Factors that may predispose to seizures:
Family history
Prenatal and perinatal factors
Trauma and surgery
Metabolic causes
Toxic causes (drugs, withdrawal of antiepileptics,
chronic alcohol abuse, CO, Pb, Hg)
Infectious and inflammatory causes
Vascular causes
Intracranial tumours
Hypoxia
Degenerative diseases
Photosensitivity and sleep deprivation
Pathophysiology
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Large groups of neurons activated
repetitively and hypersynchronously
with dysfunction of the inhibitory
synaptic contact between neurons
High voltage spike-and-wave
activity on EEG
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Onset of epileptic discharge may
include:
Whole cortex – primary generalized
Confined to one area fo cortex –
partial
Start focally and then spread to
involve whole cortex – secondary
generalization of a partial seizure
Clinical features
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Simple partial seizure
Focal symptoms – motor or sensory
arising from frontal motor or
parietal sensory cortex affecting
contralateral face, trunk or limbs
No loss of consciousness
Structural brain lesion must be
excluded (stroke, tumour or
abscess)
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Complex partial seizure
Originate in temporal or frontal lobe
– complex auras
Partial clouding of consciousness
Absence seizure
Onset between 4-12y
May occur several times/day, 5-15 s
duration
Patient suddenly stares vacantly
May be eye blinking or myoclonic
jerks
Tonic-clonic seizure (grand mal)
• 2 incidence peaks – children/ 5-6th
decade
• Sudden loss of consciousness and fall to
the ground
• Tonic phase: lasts +/- 10s, body stiff,
elbows flexed, legs extended; breathing
stops (cyanosis); loss of bladder/bowel
function
• Clonic phase: lasts 1-2min, violent
generalized rhythmical shaking; eyes roll
back, tongue may be bitten, tachycardia
Breathing recommences at the end of clonic
phase!
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Investigations and diagnosis
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Brain imaging
EEG
Blood tests
Diagnosis of seizure:
Pupil dilatation
Raised blood pressure and heart rate
Extensor plantar responses
Central and peripheral cyanosis
Generalized – PO2 and pH and CK and
serum prolactin
Differential diagnosis
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Syncope – prodromal pallor, nausea,
sweating and palpitations (vasovagal
attacks, arrhythmias, carotid sinus
syndrome, postural hypotension)
Non-epileptic seizures – psychologically
determined, attention-seeking feigned
TIA – transient loss of consciouness when
posterior circulation involved
Hypoglycaemia – behavioural
disturbances and seizures
Drug treatment
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When 2/+ unprovoked seizures occured in a short
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Whenever possible use only 1 drug to avoid
interactions
Anticonvulsants
carbamazepine, Na valproate, lamotrigine,
phenytoin
2nd line: gabapentin, levetiracetam,
phenobarbitone
Generalized in adults: Na valproate or lamotrigine
Absence in children: ethosuximide or Na valproate
Partial seizures: carbamazepine or lamotrigine
PARKINSON’S DISEASE
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Extrapyramidal condition
characterized by disorders of
movement – diminished movement
with increased tone, AKINETICRIGID SYNDROME
caused by lesions of basal ganglia
and their connections
1:200 over 70y (++ men)
Pathology
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Proressive degeneration of cells
within the pars compacta of
substantia nigra in the midbrain
Eosinophillic inclusions (Lewy
bodies) found in surviving neurons
Loss of dopamineric cells in
substantia nigra – reduction of
dopamine in striatum
Aetiology
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Unknown
Possible genetic component
Familial (?) – mutations in alphasynuclein and Parkin gene
Exogenous toxins (MPTP
contamined heroin)
Clinical features
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Tremor, rigidity and bradykinesia
(asymmetrically striking) associated
with changes in posture and gait
Tremor – coarse resting tremor (4-7
Hz), decreased by use, increased by
emotion/ distraction; disappears
during sleep; pin-rolling nature; ++
affects hands, feet (tongue, chin)
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Rigidity – stiffmess of limbs felt
throughout the range of movement and
equally on flexors and extensors
Bradykinesia – slowly and poverty of
movements affecting not only the limbs
but also the muscles of facial expression
(stone facies)
Postural changes – stooped posture,
shuffling, flexed and festinant gait with
poor asymmetrical arm swing (move “en
bloc”)
Speech - hypophonic dysarthria
Cognitive function preserved in early
stages
Constipation and urinary difficulties
Differential diagnosis
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Drugs – dopamine antaonists
(phenothiazines, reserpine,
haloperidol)
Trauma (repetitive head injury)
Cerebrovascular disease (lacunar
infarcts of BG)
Toxins
Other akinetic-rigid syndromes
Drug treatment
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AIM: restore dopamine levels within
striatum
L-dopa – symptomatic treatment
combined with a peripheral decarboxylase
inhibitor (carbidopa) to reduce SE
(nausea, vomiting, hypotension)
Improves bradykinesia and rigidity, little
effect on tremor
Should not be started until ansolutely
necessary!!! (start w/ dopamine agonist)
With time, duration of drug action
reduces – “on-and-off syndrome”
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Dopamine agonist – pergolide and apomorphine;
analogues of dopamine that directly stimulate
dopamine receptors (most effective on D2)
Anticholinergic drugs – benzhexol, bentropine;
penetrate CNS, reduce tremor (SE: dry mouth,
constipation, urinary retention, hallucinations,
confusion)
Selegiline – inhibitor of MAO B, block degradation
of dopamine in CNS
COMT antagonists – entacapone; prevent COMT
mediated dopamine breakdown and increase
dopamine availability centrally
Surgery – severe cases and young patients;
stereotactic thalamotomy, pallidotomy,
transplantation of fetal substantia nigra and
subthalamic neurostimulators
Thank you for your
attention!