Parkinson`s Disease

 

1817 Paralysis agitans

 

 

Aetiology

Exposure to toxic agents, eg insecticides, herbicides

Minute doses of MPTP

Subtle genetic factor

Head trauma

Encephalitis

Idiopathic

Cigarette smoking is probably protective

 

 

Clinical features

Progressive onset of features in late middle life

Progression over 10 - 15 years

1 in 200 people over 70 years

 

Rigidity, lead pipe and/or cog wheel

Tremor, 4-7 Hz.

Bradykinesia

Pill rolling

Speech becomes monotonous

Constipation common

Postural changes, e.g. stoop and shuffling gait

Balance is impaired

Mask like expression

Gastrointestinal symptoms 

Urinary difficulties

 

Depression is common and dementia may occur

Diagnosis is on clinical grounds only

Early onset cases usually have a poorer prognosis

 

Pathophysiology

Loss of dopaminergic neurones of the substantia nigra

Imbalance between acetylecholine and dopamine 

This correlates well with cell loss and degree of akinesia.

 

 

Treatment

Anticholinergics eg benzhexol

Dopamine agonists, eg. levodopa.

 

Clinical forms

Idiopathic

Drug induced

Post-encephalitic

 

Pharmacology

Levodopa is a precursor of dopamine.

After a few years unpredictable fluctuations in mobility occur.

Given with carbidopa to reduce side effects.

 

MAO B normally degrades dopamine.

May be used with levodopa.

MAO B inhibitors (e.g. selegiline) prevent breakdown of dopamine.

 

Dopamine receptor agonists (e.g. bromocriptine).

Reduce dependency on the degenerating presynaptic neurones.

 

Anticholinergics (orphenadrine, procyclidine), inhibit action of acetylecholine.

Acetylecholine receptor antagonists.

Relieve mild tremor and stiffness but do not improve akinesia.

 

Multiple Sclerosis

 

 

Aetiology

15 - 20 times more common in first order relatives

More common in monozygotic twins

Autoimmunity

 

 

Theories

Infection          

Abnormality in myelin lipid constituents

High animal fat diet

An autoimmune disorder of the central nervous system resulting from an environmental stimulus in genetically susceptible individuals.

 

Epidemiology

1 in 800 people in the UK, 50 000 people affected         

More common in women than men

Temperate climates

Onset usually 20 - 40 years

 

Pathology

Multiple areas of demyelination only within the brain and spinal cord

Areas of demyelination are disseminated in time and place

Areas of demyelination are initially 2 - 10 mm in size

Inflammatory changes

Phagocytosis of myelin

Defect is in the oligodendroglial cells    

Gliosis forms a chronic plaque

Remyelination seldom occurs

 

Clinical features

Three forms

Relapsing and remitting 90%     

Primary progressive     

Secondary progressive

 

Many first present with retrobulbar neuritis giving blurred vision, areas of visual loss and pain associated with eye movements - recovery is typical after a month

Fatigue                                    

Spasticity

Diplopia (double vision), vertigo, nystagmus     

Limb weakness

Severe, but variable sensory disturbances, resulting in loss of muscle control.

Tingling, stiffness and later problems walking.

Bladder disturbances

Ataxia              

Slurred speech

Undue fatigue              

Intellectual and affective disturbances

Impotence                    

Nausea                                                                        

Evolution varies greatly between patients

End result may be tetraplegia

Typical life expectancy is 30 years

 

Diagnosis

MRI is the first line investigation

Exclusion of other pathology

Delayed visual - evoked responses

Improvement with ACTH

CSF - inflammatory cells, increased proteins and immunoglobulins, oligoclonal IgG

 

 

 

 

Management 

 

Drugs

ACTH (Adrenocortiotrophic Hormone), usually for four weeks

Methile Prednisolone, usually one IV injection per day x 3

Other steroids, (do not influence long term outlook)

Beta interferon - reduces the attack rate by one third and reduces number of lesions

Immunosupressants, eg. Azothioprine

Muscle relaxants eg. baclofen

Anti-emetics

Cannabis

 

General measures

Prevent complications of immobility

Physiotherapy, active and passive exercise.

Occupational therapy

Management of intercurrent infections, eg UTI

Honesty

 

 

 

 

 

 

 

Pharmacology

 

Interferon beta – 1a and 1b are

immunomodulators

 

Prevent frequency and severity

Of relapses in relapsing and

remitting MS

 

May interrupt immune activation

and reduce tissue damage

 

 

 

 

Corticosteroids

 

Cell membrane phospholipid released into tissues

 

Phospholipase A (Corticosteroids inhibit the activity of this enzyme)

 

Arachidonic acid

 

Cyclo-oxygenase COX (NSAIDs and aspirin inhibit COX activity)

 

Prostaglandins

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Motor Neurone Disease

 

Aetiology

Idiopathic

Usually sporadic

? Viral infection

? Trauma

? Electric shock

? Exposure to toxins

Occurs worldwide

5 – 10% of cases familial

 

 

Epidemiology

Prevalence of about 5 per 100 000

Usually over 50, uncommon below 30 years

 

 

Pathology

Cellular apoptosis of all motor areas of CNS and PNS

Upper and lower motor neurones die

 

Clinical features

Brisk reflexes in a fasiculating wasted limb

Limb weakness

Muscle atrophy, weakness and stiffness, often hands and feet first working through to arms and legs

Cramps may occur but there is no pain

Weakness in tongue and face

Progressive bulbar palsy

Cranial nerves are most severely affected

Dysarthria

Dysphagia

Nasal regurgitation

Choking

 

No sensory or cognitive features

Remission does not occur, relentless progress of the disease

 

Complications

Complications of immobility

Respiratory infection

Weak respiratory muscles leading to respiratory failure

 

Diagnosis

Clinical diagnosis only

Electromyography

 

 

Symptomatic management

Riluzole is antiglutamate

Prevent complications of immobility

Prevention of cramps

Prevention of aspiration

PEG (percutaneous gastrostomy

Non invasive ventilatory support

Invasive ventilation if patient chooses to do so

OT, Physio, Speech Therapist

These patients are usually well informed and are aware of the prognosis

Spiritual, psychological support

Death from pulmonary infection and inhalation usually occurs in about three years.

Opiates and sedation for terminal distress                                                                      ALS

 

 

 

Huntington`s Disease

 

 

Aetiology

Autosomal dominant - distal short arm of chromosome 4

 

Triplet (tri nucleotide) repeat disorder

 

More  nucleotide triplets means more glutamines

 

Occurs worldwide, 5 in 100 000

 

 

Pathology

 

Abnormal Huntington protein accumulates in neurones leading to cell death

 

Anticipation phenomena means the age of onset is younger in succeeding generations, progressive expansion of the repete

 

Cerebral atrophy

 

Loss of small neurones in caudate and putamen (large lateral basal ganglia below the thalamus)

 

Imaging shows atrophy of the caudate nucleus and putamen

 

Basal galglia are part of extrapyramidal system

 

Cerebral chemical abnormalities, e.g. lack of acetylcholine in the striatum, lack of

 

GABA in the substantia nigra

 

 

Clinical features

 

Features usually present in mid life

 

Progressive chorea, jerky, quasi-purposive, may be fidgety

 

Psychiatric symptoms which progress on to dementia

 

Seizures later on

 

Death occurs in 10 – 20 years

 

Many patients have already had children

 

 

Diagnosis

 

Clinical

 

CT MRI

 

Genetic testing

 

 

Treatment

 

Symptomatic only

 

Some drugs for chorea

 

Depression is common and responds to usual treatment

 

Genetic counselling

 

 

Brain tumours

 

Cerebral tumours account for 2% of deaths at all ages.

Metastatic are the most common form in the UK, most commonly from primaries in the bronchus, breast, GI

Malignant cerebral tumours do not metastasise outside of the CNS

Primary classified by their cells of origin.

Glial cells or neuroglial cells

 

Gliomas

Spread by direct invasion

Astrocytomas may grow rapidly

Oligodendrogliomas grow slowly

 

Meningiomas

Benign

Arise from the arachnoid

May become very large over years

 

Neurofibromas

Arise from Schwann cells of the VIII cranial nerve

Acoustic neuroma

 

Others

Haemangioblastoma is uncommon

Pituitary tumours

 

Invesigations

CT, MRI

CXR to look for primary

 

Clinical features

Direct effects, focal neurological defects, slow in onset and progressive.

 

Small tumour present early in brain stem, large ones will may develop in the frontal lobes.

 

Oedema around a tumour may cause rapid presentation of symptoms.

 

Tumours often present with seizures, generalised of partial seizures.

 

Partial seizures developing in adult life should always suggest a tumour.

 

Increased intracranial pressure with nausea, vomiting, headache, drowsiness, confusion, impairment of consciousness, papilloedema and eventually bradycardia, hypertension

 

Headache not always. RICP --- traction of sensitive pain sensitive intracranial structures.

 

Eventual coning

 

 

Medical Management

Dexamethasone 8 mg / 12 hourly to take away oedema so lowering ICP

Improves level of consciousness and reduces focal disability

Higher doses may be given IV, say 16 – 20 mg

Anticonvulsants

Radiotherapy and chemotherapy have only marginal effect on survival. But good for selected pathologies and in children

 

 

Surgical management

Mainstay

Meningiomas, fully resected

Gliomas can be debulked

Prognosis depends on histological grade, I-II may survive for years, but grade IV gliomas only 1 year.

 

 

 

 

 

 

Neurological Diseases MCQs

 

1. Which of the following statements is true of Parkinson’s disease?

(Chose 1 correct answer).

a. too much dopamine is produced

b. not enough acetyle choline is produced

c. too little dopamine is produced

d. giving dopamine metabolic precursors has no effect on the clinical features

 

2. Disorder in which part of the brain leads to the clinical features of Parkinson’s disease?

(Chose 2 correct answers)

a. basal ganglia

b. occipital lobe

c. frontal lobe

d. medulla oblongata

e. hypothalamus

f. substantia nigra

g. temporal lobe

 

3. Which of the following clinical features indicate the presence of Parkinson’s disease?

 (Chose 5 correct answers)

a. bradykinesia

b. bradycardia

c. muscular rigidity

d. tachypnoea

e. intention tremor

f. shuffling gait

g. hypoglycaemia

h. mask like expression

 

4. Parkinson’s disease effects which of the following systems?

(Chose 1 correct answer).

a. reticular activating system

b. Haversian system

c. pyramidal system

d. extrapyramidal system

f. limbic system

g. peripheral nervous system

 

5. ‘Idiopathic’ aetiology means the cause of a disease is,

(Chose 1 correct answer).

a. viral

b. bacterial

c. autoimmune

d. uncertain

e. traumatic

f. degenerative

g. environmental

 

6. Parkinson’s disease should be suspected in a patient presenting with,

(Chose 1 correct answer).

a. irregular pulse, chest pain, palpitations

b. unequal pupils, decreased GCS, lateralising signs

c. hemiparesis, dysphasia, hemianesthesia

d. psychiatric problems, jerky movements, progressive chorea

e. resting tremors, decreased movement, rigidity

f. muscle wasting, bilateral weakness, swallowing difficulties

 

7. The aetiology of multiple sclerosis is probably,

(Chose 1 correct answer).

a. lack of vitamin A

b. a type 1 hypersensitivity reaction

c. infection with streptococcus

d. infection with staphylococcus

e. lack of myelin in the diet

f. an autoimmune T cell mediated reaction

 

8. In multiple sclerosis there is loss of,

(Chose 1 correct answer).

a. Schwann cells in the peripheral nervous system

b. oligodendroglial cells the central nervous system

c. dopamine in the substantia nigra

d. neurones from the cerebral cortex

e. blood supply to one side of the brain

f. of proteins in the urine

 

9. The most common form of multiple sclerosis is,

(Chose 1 correct answer).

a. primary progressive

b. secondary progressive

c. relapsing and remitting

d. thromboembolic

e. haemorrhagic

f. infratentorial

 

10. Typically in MS it will be seen that,

(Chose 2 correct answers).

a. there are motor but no sensory features

b. there are sensory but no motor features

c. swallowing is usually effected first

d. only one side of the body will be effected

e. there are multiple neurological deficits

f. lesions are separated by time and space

 

11. Possible treatments used in MS might be,

(Chose 2 correct answers).

a. codeine

b. anitcholinergics

c. steroids

d. thrombolytics

e. antiplatelet drugs

f. interferons

g. dopamine precursor molecules

 

12. Motor neurone disease should be suspected in a patient presenting with,

(Chose 1 correct answer).

a. irregular pulse, chest pain, palpitations

b. unequal pupils, decreased GCS, lateralising signs

c. hemiparesis, dysphasia, hemianesthesia

d. psychiatric problems, jerky movements, progressive chorea

e. resting tremors, decreased movement, rigidity

f. muscle wasting, fasiculation, swallowing difficulties

 

 

 

13. Which of the following is likely to present in motor neurone disease

(Chose 1 correct answer).

a. dysphasia

b. dysmenorrhoea

c. disarticulation

d. dysuria

e. dysarthria

f. dyslexia

 

14. Typically in motor neurone disease the disease evolution will

(Chose 1 correct answer).

a. relentlessly progress

b. show relapses and remissions

c. remain stable for several years

d. gradually improve over time

 

15. Apoptosis describes,

(Chose 1 correct answer).

a. somatic cell division

b. production of gametes

c. uncontrolled cell division

d. normal cell division

e. cell suicide

 

16. In bulbar palsy you will expect to see,

(Chose 3 correct answers).

a. weakness in the hands

b. weakness in the legs

c. dysarthria

d. disphagia

e. dyspnoea

f. bradycardia

g. aspiration

h. dysphasia

 

17. Huntington’s disease could be suspected in a patient presenting with,

(Chose 1 correct answer).

a. irregular pulse, chest pain, palpitations

b. unequal pupils, decreased GCS, lateralising signs

c. hemiparesis, dysphasia, hemianesthesia

d. psychiatric problems, jerky movements, progressive chorea

e. resting tremors, decreased movement, rigidity

f. muscle wasting, fasiculation weakness, swallowing difficulties

 

18. The aetiology of Huntington’s disease is,

(Chose 1 correct answer).

a. sex linked on the X chromosome

b. sex linked on the Y chromosome

c. caused by a single gene deletion

d. autosomal recessive

e. autosomal dominant

f. caused by a congenital abnormality

 

 

 

 

 

 

19. In Huntington’s disease the clinical signs normally present,

(Chose 1 correct answer).

a. at birth

b. during childhood

c. at adoleceence

d. in young adult life

e. in late middle age

f. in old age

 

20. The part of the nervous system usually effected first in Huntington’s disease is the ,

(Chose 1 correct answer).

a. Schwann cells

b. oligodendroglial cells

c. motor neurones

d. sensory neurones

e. motor cortex in the pre-central gyrus of the frontal lobe

f. sensory cortex in the post central gyrus of the parietal lobe

g. basal ganglia

h. substantia nigra

i. spinal cord

 

21. Most primary brain tumours arise from which type of cells,

(Chose 1 correct answer).

a. motor neurones

b. sensory neurones

c. glial cells

d. blood vessel endothelium

e. osteoblasts

f. osteoclasts

 

22. Which clinical features, presenting in an adult may indicate the presence of a brain tumour,

(Chose 3 correct answers).

a. a localised fit

b. a generalised fit

c. schizophrenia

d. depression

e. papilloedema

f. chest pain

g. an irregular pulse

 

23. Why is dexamethasone often used in patients with brain tumours, it;

(Chose 1 correct answer).

a. is cytotoxic, so reduces tumour size

b. reduces the rate of mitosis in tumour cells

c. will cure most brain tumours

d. is an analegesic, so reduced pain

e. is anti-inflammatory so reduced oedema

f. promotes the inflammatory response so aids the immune system