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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 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 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, AKINETICRIGID 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 alphasynuclein 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!
