Neurology

The ageing brain and nervous system

As in other systems intrinsic ageing (occurs in all) is often hard to distinguish from extrinsic ageing mechanisms (caused by disease processes). See

‘Cognitive ageing’, p.204 for discussion of cognitive ageing.

Histological changes in the brain include:

Each neuron has fewer connecting arms (dendrites)
Around 20% of brain volume and weight are lost by the age of 85
There is deposition of pigment (lipofuscin) in the cells and oxidative damage in mitochondria
The presence of senile plaques and neurofibrillary tangles increases with age but they are not diagnostic of dementia (Table 7.1)

Table 7.1 Age-related changes to the nervous system

Age-related change	Consequence
Loss of neurons (cannot be regenerated) Decrease in brain weight (by around 20% at age 85)	Cerebral atrophy common on brain scans (although this does not correlate well with cognitive function)
Some neurons become demyelinated and have slowed nerve conduction speed and increased latency (time taken to recover before transmitting next impulse)	Reflexes which have long nerve tracts, eg ankle jerks, can be diminished or lost
	Minor sensory loss, eg fine touch/vibration sense, may be lost distally
Neurotransmitter systems alter, eg cholinergic receptors decrease	Increased susceptibility to some neuromodulating drugs
Increasing frequency of periventricular white matter changes seen on cerebral imaging	Probably not a normal finding
	Significance unclear—assumed to be representative of small-vessel vascular disease but poor postmortem correlation

Tremor

Tremor is more common with increasing age. It can be disabling and/or socially embarrassing. It is important to try to make a diagnosis as treatment is available in some cases.

Examine the patient first at rest and distracted (relaxed with arms supported on lap, count backwards from 10), then with outstretched hands and finally during movement (pointing or picking up a small object). Tremors fall roughly into three categories

Rest tremor—disappears on movement and is exaggerated by movement of the contralateral side of the body. Commonest cause— Parkinson’s disease. It is usually associated with increased tone
Postural tremor—present in outstretched limbs, may continue during action but disappears at rest. Commonest cause—benign essential tremor
Action tremor—exaggerated with movement. When the tremor is maximal at extreme point of movement it is called an intention tremor. Commonest cause—cerebellar dysfunction

Benign essential tremor

The classic postural tremor of old age, worse on action (eg static at rest but spills tea from teacup) may have head nodding (titubation) or jaw/vocal tremor, legs rarely affected. May be asymmetrical
About half the cases have a family history (autosomal dominant)
Presents in middle age, occasionally earlier and worsens gradually
Often more socially embarrassing than physically impairing
Improved by alcohol, gabapentin, primidone and β-blockers but these often unacceptable treatments in the long term. Worth considering β-blockers as first choice in treatment with coexistent hypertension
Weighted wristbands can reduce tremor and improve function

Parkinson’s disease (see

‘Parkinson’s disease: presentation’, p.158)

Cerebellar dysfunction

The typical intention tremor is associated with ataxia.

Acute onset is usually vascular in older patients
Subacute presentations occur with tumours (including paraneoplastic syndrome), abscesses, hydrocephalus, drugs (eg anticonvulsants), hypothyroidism or toxins
Chronic progressive course is seen with:
- Alcoholism (due to thiamine deficiency—always give thiamine 100mg od orally or iv preparation if in doubt, it might be reversible)
- Anticonvulsant (eg phenytoin—may be irreversible if severe, commoner with high plasma levels but can occur with long-term use at therapeutic levels)
- Paraneoplastic syndromes (anti-cerebellar antibodies can be found, eg anti-Yo and anti-Hu found in cancer of ovary and bronchus)
- Multiple sclerosis
- Idiopathic cerebellar atrophy
- Many cases defy specific diagnosis. Consider multisystem atrophy

Other causes of tremor (Table 7.2)

Table 7.2 Other causes of tremor

Diagnosis	Recognition and characteristics	Management
Thyrotoxicosis	Fine resting tremor This is actually commoner in younger patients	See ‘Hyperthyroidism: drug treatment’, p.442
Rigors	Sudden onset coarse tremor with associated malaise and fever	Diagnose and treat underlying cause
Asterixis (tremor and incoordination) with hepatic, renal or respiratory failure	Coarse postural tremor in a sick patient with physiological disturbance A less dramatic, often fine, tremor can occur with metabolic disturbance such as hypoglycaemia or hypocalcaemia	Diagnose and treat underlying condition
Drug withdrawal, eg benzodiazepines, SSRIs, barbiturates	Always consider when patient develops tremor ± confusion soon after admission	For therapeutic drugs recommence and consider gradual controlled withdrawal at later date
Alcohol withdrawal	Always take an alcohol history. Tremor ± confusion develops soon after admission	Consider treatment with, eg chlordiazepoxide and thiamine
Drug side effects, eg lithium, anticonvulsants		Check serum levels are in therapeutic range. Consider a different agent
Anxiety/stress— increased sympathomimetic activity	Fine tremor	Rarely necessary to consider β-blockers
Orthostatic tremor—rare, benign postural tremor of legs	Fine tremor of legs on standing diminished by walking/sitting. Can palpate muscle tremor in legs. Patient feels unsteady but rarely falls	Provide perching stools etc to avoid standing for long

Neuropathic pain/neuralgia

This describes pain originating from nerve damage/inflammation. It is often very severe and debilitating and seems to be more common in older people. The pain is usually sharp/stabbing and is often intermittent being precipitated by things like movement and cold.

Post-herpetic neuralgia

Severe burning and stabbing pain in a division of nerve previously affected by shingles
Shingles and subsequent persisting neuralgia is much more common in older patients
Pain may be triggered by touch or temperature change
May go on for years, be difficult to treat and have major impact on quality of life
Prevent by starting antivirals within 72hr of rash (eg famciclovir)
See ‘HOW TO … Treat neuralgia’, p.157 for treatment

Trigeminal neuralgia

Severe unilateral stabbing facial pain, usually V2, V3 rather than V1
Triggers include movement, temperature change, etc.
Time course—years with relapse/remission
Depression and weight loss can result
Differential diagnoses include temporal arteritis, toothache, parotitis and temporomandibular joint arthritis
Consider neuroimaging especially if there are physical signs, ie sensory loss or other cranial nerve abnormality suggestive of secondary trigeminal neuralgia
Bilateral trigeminal neuralgia suggests multiple sclerosis
See ‘HOW TO … Treat neuralgia’, p.157 for treatment

Neuralgia can also occur with

Malignancy
Cord compression
Neuropathy

HOW TO … Treat neuralgia

This can be very debilitating and treatment is difficult. There is often coexistent depression, so always think of this and treat appropriately.

Simple measures include

Distraction
Relaxation techniques
Allaying fears (usually about serious underlying pathology)
Acupuncture
Heat/cold treatment
Osteopathy/massage (to reduce associated muscle spasm)
Use of TENS machines (transcutaneous nerve stimulation)
Support groups, eg www.tna.org.uk

Medications

Topical treatments, eg lidocaine, capsaicin
Traditional analgesics (paracetamol, NSAIDs, opiates) although these are usually not very effective
Anti-spasticity drugs, eg baclofen. Used especially in trigeminal neuralgia, they treat any muscle spasm that exacerbates the pain

Mainstay of treatment is the neuromodulating drugs which may give superior pain control but often have important side effects.

Examples include:

Antidepressants with neuroadrenergic modulating abilities,

eg amitriptyline, duloxetine. Start with a low dose and titrate up slowly. Eventual doses may be similar to those used in younger patients
Anticonvulsants, eg gabapentin, pregabalin (postherpetic neuralgia) or carbamazepine, oxcarbazepine, valproate (trigeminal neuralgia). Start with a low dose and titrate up slowly

The main side effects from these drugs are sedation and confusion, and reaching a therapeutic dose may be limited by this problem.

Other options

Nerve blocks or spinal stimulation, which can usually be accessed via a specialist pain clinic
Surgery, eg nerve decompression, or treatment with heat or lasers. May provide relief but can result in scarring and numbness

Parkinson’s disease: presentation

A common, idiopathic disease (prevalence 150/100 000) associated with inadequate dopamine neurotransmitter in brainstem. There is loss of neurons and Lewy body formation in the substantia nigra. The clinical syndrome is distinct from Lewy Body dementia (See

‘Dementia and parkinsonism’, p.214 for treatment) but there is overlap in some pathological and clinical findings leading to suggestions they might be related conditions.

Presentation

The clinical diagnosis of Parkinson’s disease is based on the UK Parkinson’s disease brain bank criteria and should include:

Bradykinesia (slow to initiate and carry out movements, expressionless face, fatigability of repetitive movement)

Plus at least one of the following:

Rigidity (cogwheeling = tremor superimposed on rigidity)
Tremor (‘pin-rolling’ of hands—worse at rest)
Postural instability

Other clinical features:

Gait disorder (small steps)
Usually an asymmetrical disease
No pyramidal or cerebellar signs but reflexes are sometimes brisk
Non motor symptoms are common and should be asked about (see ‘Non-motor symptoms of Parkinson’s disease’, p.158)

Non-motor symptoms of Parkinson’s disease

Depression (treat appropriately)
Psychosis (may relate to medications; avoid typical antipsychotics as they may worsen the motor features; atypicals such as quetiapine or olanzapine can be tried)
Dementia and hallucinations can occur in late stages but drug side effects can cause similar problems. If features suggest Lewy body dementia a trial of anticholinesterases may be warranted
Sleep disturbance (treat restless legs, review medications, advise about driving if sudden onset sleep, daytime hypersomnolence may be treated with modafinil)
Falls (usually multifactorial, see ‘Assessment following a fall’, p.104)
Autonomic features are generally late features, but common in older patients. They should be sought and actively managed:
- Weight loss
- Dysphagia
- Constipation
- Erectile dysfunction
- Orthostatic hypotension
- Excessive sweating
- Drooling

Investigations

Diagnosis is clinical, and once suspected should be reviewed by a Parkinson’s disease specialist
Trials of treatment may be done, with review of the diagnosis if there is no improvement, but single dose levodopa ‘challenge’ tests are no longer performed
Brain imaging (eg CT) can be used to illustrate other conditions that may mimic Parkinson’s disease (eg vascular disease)
Specialist scans are becoming more widely used to assist diagnosis

(eg consider ¹²³I-FP-CIT single photon emission computed tomography (SPECT), commonly known as DatSCAN™ after the radiolabelled solution used)

Parkinson’s disease: management

Should be overseen by a Parkinson’s disease specialist clinic.

Drugs

It is not possible to identify a universal first-choice drug therapy for either early Parkinson’s disease or for adjuvant drug therapy for later stages.

Consider the short- and long-term benefits and risks of each treatment, along with lifestyle and clinical factors. Discussion with the patient is key.

Initiation treatment is started with one of the following:

Levodopa plus decarboxylase inhibitor (prevents peripheral breakdown of drug) (co-beneldopa/co-careldopa). Start low and titrate to symptoms
Dopamine agonists (ropinirole, pergolide, cabergoline). Psychiatric side effects, postural hypotension and nausea often limit therapy
MAOI (selegiline). The newer buccally absorbed preparation is better tolerated and useful in swallowing difficulties. These drugs have many interactions with antidepressants and should be used with care by a specialist

Adjuvant treatment may be needed as the disease progresses. Firstly increase doses or add a second agent from the list already given then consider:

COMT inhibitor (entacapone). Will smooth fluctuations in plasma levodopa concentrations. Give with each levodopa dose—sometimes will need levodopa dose decrease. Stains urine orange
Amantadine—weak dopamine agonist which can reduce dyskinetic problems
Apomorphine—subcutaneous (s/c) injections. Specialist treatmentrarely useful in older patients except to cover periods of nil by mouth

Anticholinergics (benzhexol, orphenadrine) are mild anti-parkinsonian drugs rarely useful in elderly patients due to severe psychiatric side effects. They do have a beneficial effect on tremor and are possibly the drug of choice where tremor is more of a problem than bradykinesia.

Surgery

Ablation (eg pallidotomy) and stimulation (electrode implants) used in highly selected populations. Older patients often excluded due to high operative risk.

Other therapeutic options

Patients and carers benefit from regular review by a specialist doctor or nurse. Many services now have specialist Parkinson’s disease nurses
A course of physiotherapy can be helpful to boost mobility
Occupational therapy plays a vital role in aids and adaptations for disability
Speech and language therapists, along with dieticians can help when swallowing becomes a problem
Occasionally inpatient assessment is helpful but be aware that hospital routines can rarely match home treatment and some patients deteriorate in hospital
Parkinson’s UK ( www.parkinsons.org.uk) has plenty of information and advice for patients and carers

HOW TO … Manage a patient with Parkinson’s disease who cannot take oral medication

This situation arises quite commonly in advanced disease during a hospital admission.

A patient with advanced disease, admitted for another reason (eg sepsis) may miss an oral dose of medication (eg because they are unwell, or because the drug is not immediately available). In some this will be well tolerated; in others there will be a rapid decline in function and loss of swallow, with a downward spiral unless promptly managed.

Other situations in which oral medication may not be possible:

Perioperatively when patient is nil by mouth
When an ileus or other cause makes poor drug absorption likely
After a stroke

▶Omission of medication will (for most patients with Parkinson’s disease) lead to a decline in function, so continuation of treatment is key.

Reducing the risk

Plan ahead—patients should be educated about the importance of taking medication on time, and always bring their own medication with them if they come into hospital and be encouraged to self medicate where possible
If surgery is elective, then get specialist advice about medication as part of the preoperative assessment. Aim for local or regional anaesthesia if possible
Have protocols in place for the urgent care of Parkinson’s disease patients
Ensure that wards have Parkinson’s disease drugs readily available

Early action

Use nasogastric (NG) tubes early if swallow is impaired
Relax nil by mouth rules preoperatively for Parkinson’s disease drugs
Use antiemetics when vomiting

Medication

Use a different preparation eg levodopa dispersible down an NG tube, buccal selegiline
Use an enteral preparation eg apomorphine (subcutaneous delivery) or rotigotine (patch delivery). Advice will be needed from a specialist about doses that are equivalent to their usual medication