DEGENERATIVE NEURONAL DISEASES

Motor neurone disease

There is relentless and unexplained destruction of upper motor neurones and anterior horn cells in the brain and spinal cord. Most patients die within 3 years from respiratory failure as a result of bulbar palsy and pneumonia. It presents in middle age and is more common in men. Most cases are sporadic with no family history but the rare familial cases may give clues to the pathophysiology. Mutations in the free radical scavenging enzyme, copper/ zinc superoxide dismutase (SOD-1), are responsible for one familial form suggesting that oxidative stress and free radicals are implicated in the destruction of motor neurones.

Clinical features

Four clinical patterns are seen at diagnosis. However, as the disease progresses most patients develop a mixed picture. There is no involvement of the sensory system or motor nerves to the eyes and sphincters in any of the clinical types:

■ Progressive muscular atrophy is a predominantly lower motor neurone lesion of the cord causing weakness, wasting and fasciculation (sponta-neous, irregular and brief contractions of part of a muscle) in the hands and arms.

■ Amyotrophic lateral sclerosis is a combination of disease of the lateral corticospinal tracts and anterior horn cells producing a progressive spastic tetraparesis or paraparesis with added lower motor neurone signs (wasting and fasciculation).

■ Progressive bulbar and pseudobulbar palsy results from destruction of upper (pseudobulbar palsy) and lower (bulbar palsy) motor neurones in the lower cranial nerves. There is dysarthria, dysphagia with wasting, and fasciculation of the tongue.

■ Primary lateral sclerosis is rare. There is progressive tetraparesis.

Investigations

The diagnosis is clinical; fasciculation is characteristic. An EMG shows muscle denervation, but this is not a specific finding.

Differential diagnosis

The differential diagnosis is a cervical spine lesion, which may present with upper and lower motor neurone signs in the arms and legs. It is often dis-tinguished by the presence of sensory signs. Idiopathic multifocal motor neuropathy (Table 17.19) presents with weakness predominantly in the hands and profuse fasciculation.

Management

Riluzole, a sodium-channel blocker that inhibits glutamate release, slows progression slightly. Ventilatory support and feeding via a PEG (p. 124) helps prolong survival for some months.

Table 17.19 Causes of mononeuritis multiplex

Diabetes mellitus

Leprosy (the most common cause world-wide)

Vasculitis

Sarcoidosis

Amyloidosis

Malignancy

Neuroíibromatosis

HIV infection

Guillain-Barré syndrome

Idiopathic multifocal motor neuropathy (distal motor, unknown cause)

Spinal muscular atrophies

This is a group of rare disorders which destroy the anterior horn cells of the spinal cord. There is a slowly progressive, usually symmetrical wasting and weakness of the limbs.

Dementia

Dementia describes progressive decline of cognitive function, i.e. loss of mind, usually affecting the cerebral cortex as a whole, though sometimes patchily. Consciousness is not, however, clouded. Dementia affects about 10% of those aged 65 years and over, and 20% of those over 80. The com-monest causes are Alzheimer’s disease, fronto-temporal dementia, vascular dementia and dementia with Lewy bodies (Table 17.20).

Alzheimer’s disease

Alzheimer’s disease is a primary degenerative cerebral disease of unknown aetiology and accounting for over 65% of dementia in any age group. There are characteristic pathological features, which include neuronal reduction in several areas of the brain, neurofibrillary tangles, argentophile plaques, con-sisting largely of amyloid protein, and granulovacuolar bodies.

Clinical features

There is an insidious onset with steady progression over years. Short-term memory loss is usually the most prominent early symptom, but subsequently there is slow disintegration of the personality and intellect, eventually affect-ing all aspects of cortical function. There is decline in language (difficulty in naming and in understanding what is being said), visuospacial skills, apraxia (impaired ability to carry out skilled motor tasks) and agnosia (failure to recognize objects, e.g. clothing, people, places).

Table 17.20 Causes of dementia
Alzheimer’s disease
Dementia with Lewy bodies
Frontotemporal dementia
Vascular dementia
Vitamin deficiency: B12, thiamin
Hypothyroidism
Intracranial mass: subdural haematoma, hydrocephalus, tumour
Chronic traumatic encephalopathy, e.g. punch drunkenness
Infections: neurosyphilis, Creutzfeldt–Jakob disease, HIV
Huntington’s disease
Parkinson’s disease

Investigations

There is no single test that will make a diagnosis of dementia. Memory problems are not always due to dementia and alternative diagnoses which mimic dementia should be considered: delirium, depression, drugs, normal age-associated memory problems. The Mini Mental State Examination (MMSE) is commonly used to screen for cognitive function. A score of 25 or above out of 30 is considered normal, score of 18 to 24 indicates mild to moderate impairment and a score of 17 or below indicates serious impair-ment. The Abbreviated Mental Test Score is a quick and simple assessment of the mental state (Table 17.21). Exclusion of rare treatable causes of dementia (Table 17.20) should also be considered and blood taken for a full blood count, liver biochemistry, thyroid function tests and measurement of vitamin B12 and folate. A brain CT scan should be performed in younger patients or those with an atypical presentation. A social and family history will help to assess how vulnerable the person is in the community and what plans for support will need to be made.

Management

In most cases there is no specific therapy, although the associated anxiety and depression often need treatment. Attempts to therapeutically augment cholinergic activity have been based on the observations that there is impaired cortical cholinergic function as a result of reduced cerebral produc-tion of choline acetyl transferase and a decrease in acetylcholine synthesis. Acetylcholinesterase inhibitors (donepezil, rivastigmine and galantamine) increase cholinergic transmission by inhibiting cholinesterase at the synaptic cleft. They have a modest benefit and slow intellectual deterioration in

Table 17.21 Abbreviated mental test score
1. Age
2. Time to nearest hour
3. Address for recall at the end of the test (house number and street name)
4. Year
5. Place – name of hospital
6. Recognition of two people (e.g. doctor, nurse)
7. Date of birth
8. Year of 1st World War
9. Name of present monarch
10. Count backwards 20 to 1
Address recall correct?
Each correct answer scores one mark.
At the 7/8 cut off sensitivity is 70–80% and specificity is 70–90% for diagnosis of dementia.

patients with mild to moderate Alzheimer's disease. Patients should be managed in the community as much as possible. A whole range of supportive interventions for both patient and carers is needed. Home care, day care, respite care and sitter services are all needed at various points during the progression of the disease. At some point long-term institutional care in a residential or nursing home may be required.

Prognosis

The typical course is one of progressive decline. The average survival is 8-10 years.

Vascular (multi-infarct) dementia

This is the second most common cause of dementia with a stepwise deterio-ration with declines followed by short periods of stability. There is usually a history of transient ischaemic attacks, although the dementia may follow a succession of acute cerebrovascular accidents or, less commonly, a single major stroke. There may be other evidence of arteriopathy.

Dementia with Lewy bodies

This is characterized by fluctuating cognition with pronounced variation in attention and alertness. Prominent or persistent memory loss may not occur in the early stages. Impairment in attention, frontal, subcortical and visuo-spatial ability is often prominent. Depression and sleep disorders occur. Recurrent formed visual hallucinations (e.g. strange faces, frightening crea-tures) are a feature. Parkinsonism (e.g. slowing, rigidity) is common, with repeated falls. Delusions and transient loss of consciousness occur. Cortical Lewy bodies are prominent at autopsy. These inclusions were first described in idiopathic Parkinson's disease, but are a hallmark of this clinical pattern of dementia. Neuroleptic drugs should not be used.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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