Common neurological conditions and their risk factors Clinical Sessions 2011 – Masaryk University...
-
Upload
kathleen-sims -
Category
Documents
-
view
219 -
download
0
Transcript of Common neurological conditions and their risk factors Clinical Sessions 2011 – Masaryk University...
Common neurological conditions and their risk factors
Clinical Sessions 2011 – Masaryk University
Vanda S. Couto Reis
Most common neurological conditions
Headache Dementias Epilepsy Movement disorders Cerebellar
dysfunction Cranial nerve lesions
Myelopathies Motor neuron
diseases Radiculopathies and
plexopathies Disorders of NMJ Vascular disorders of
nervous system
DEMENTIA
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
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
Obtain history from patient + confirm with friend / family
Neurological examination:- Focal signs- Involuntary movements- Pseudobulbar signs- Primitive reflexes (pout, grasp,
palmomental)- Gait disorders
Investigations
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
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
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
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
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
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
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
Definition: abnormal, sudden, excessive and rapid electrical discharges arising from cerebral neurons (usually self-terminating 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
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
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
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
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
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)
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!
Investigations and diagnosis
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
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
When 2/+ unprovoked seizures occured in a short period
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
Extrapyramidal condition characterized by disorders of movement – diminished movement with increased tone, AKINETIC-RIGID SYNDROME
caused by lesions of basal ganglia and their connections
1:200 over 70y (++ men)
Pathology
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
Unknown Possible genetic component Familial (?) – mutations in alpha-
synuclein and Parkin gene Exogenous toxins (MPTP
contamined heroin)
Clinical features
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)
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
Drugs – dopamine antaonists (phenothiazines, reserpine, haloperidol)
Trauma (repetitive head injury) Cerebrovascular disease (lacunar
infarcts of BG) Toxins Other akinetic-rigid syndromes
Drug treatment
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”
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!