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!