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.