Chapter 7
Neurology
The ageing brain and nervous system
Parkinson’s disease: presentation
Parkinson’s disease: management
HOW TO . . . Manage a patient with Parkinson’s disease who cannot take oral medication
HOW TO . . . Treat challenging symptoms in Parkinson’s disease
Diseases masquerading as Parkinson’s disease
Neuroleptic malignant syndrome
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. 202 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 ↑ with age, but they are not diagnostic of dementia (see Table 7.1)
Table 7.1 Age-related changes to the nervous system
Tremor
Tremor is more common with ↑ 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 the 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:
1. Rest tremor—disappears on movement and is exaggerated by movement of the contralateral side of the body. Most common cause—Parkinson’s disease. It is usually associated with ↑ tone
2. Postural tremor—present in outstretched limbs, may continue during action but disappears at rest. Most common cause—benign essential tremor
3. Action tremor—exaggerated with movement. When the tremor is maximal at extreme point of movement, it is called an intention tremor. Most common cause—cerebellar dysfunction
Benign essential tremor
• The classic postural tremor of old age, worse on action (e.g. 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 of 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 are often unacceptable treatments in the long term. Worth considering β-blockers as the first choice in treatment with coexistent hypertension
• Weighted wristbands can reduce tremor and improve function
Parkinson’s disease
see ‘Parkinson’s disease: presentation’, pp. 156–157.
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 (e.g. anticonvulsants), hypothyroidism, or toxins
• Chronic progressive course is seen with:
• Alcoholism (due to thiamine deficiency—always give thiamine 100mg once daily (od) orally (po) or iv preparation if in doubt; it might be reversible)
• Anticonvulsant (e.g. phenytoin—may be irreversible if severe, more common with high plasma levels but can occur with long-term use at therapeutic levels)
• Paraneoplastic syndromes (anti-cerebellar antibodies can be found, e.g. anti-Yo and anti-Hu found in cancer of the ovary and bronchus)
• Idiopathic cerebellar atrophy
• Many cases defy specific diagnosis. Consider multisystem atrophy
Other causes of tremor
(See Table 7.2.)
Table 7.2 Other causes of tremor
| Diagnosis | Recognition and characteristics | Management |
| Thyrotoxicosis | see ‘Hyperthyroidism: drug treatment’, pp. 442–443 |
|
| 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, e.g. 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, e.g. chlordiazepoxide and thiamine |
| Drug side effects, e.g. lithium, anticonvulsants | Check serum levels are in therapeutic range. Consider a different agent | |
| Anxiety/stress—↑ 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 vaccination to reduce risk/severity of shingles
• If shingles develops, starting antivirals within 72h reduces neuralgia incidence
see ‘HOW TO . . . Treat neuralgia’, p. 155 for treatment.
Trigeminal neuralgia
• Severe unilateral stabbing facial pain, usually V2 and 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 (TA), toothache, parotitis, and temporomandibular joint arthritis
• Consider neuroimaging, especially if bilateral or if there are physical signs, i.e. sensory loss or other cranial nerve abnormality suggestive of 2° trigeminal neuralgia
see ‘HOW TO . . . Treat neuralgia’, p. 155 for treatment.
Neuralgia can also occur with
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
• Allaying fears (usually about a serious underlying pathology)
• Osteopathy/massage (to reduce associated muscle spasm)
• Support groups, e.g. 
http://www.tna.org.uk
Medications
• Topical treatments, e.g. lidocaine, capsaicin
• Traditional analgesics (paracetamol, NSAIDs, opiates), although these are usually not very effective
• Anti-spasticity drugs, e.g. 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, e.g. amitriptyline, duloxetine. Start with a low dose and titrate up slowly. Eventual doses may be similar to those used in younger patients
• Anticonvulsants, e.g. gabapentin, pregabalin (post-herpetic 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, e.g. 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 the 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’, pp. 212–213 for treatment), but they are extremes of a clinical spectrum of disease.
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)
Other clinical features:
• 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. 156)
Non-motor symptoms of Parkinson’s disease
• Depression (treat appropriately)
• Anosmia (may be an early pre-motor feature)
• Psychosis (may relate to medications; avoid typical antipsychotics, as they may worsen the motor features; atypicals such as quetiapine 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’, pp. 102–103)
• Autonomic features are common in older patients. They should be sought and actively managed:
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 (e.g. CT) can be used to illustrate other conditions that may mimic Parkinson’s disease (e.g. vascular disease)
• Specialist scans are becoming more widely used to assist diagnosis (e.g. consider 123I-FP-CIT single-photon emission computed tomography (SPECT), commonly known as DatSCAN™ after the radiolabelled solution used). Patients with essential tremor, Alzheimer’s disease, or drug-induced Parkinsonism have normal scans
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 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 a decarboxylase inhibitor (prevents peripheral breakdown of drug) (co-beneldopa/co-careldopa). Start low and titrate to symptoms
• Dopamine agonists (ropinirole, pramipexole, rotigotine). Psychiatric side effects, postural hypotension, and nausea may limit therapy
• MAOI (selegiline, rasagiline). 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, ↑ doses or add a second agent from the list already given; then consider:
• Catechol-O-methyltransferase (COMT) inhibitor (entacapone). Will smoothe fluctuations in plasma levodopa concentrations. Must be given with levodopa. Stains urine orange
• Amantadine—weak dopamine agonist which can reduce dyskinetic problems
• Apomorphine—s/c injections. Specialist treatment—rarely useful in older patients
Anticholinergics (trihexyphenidyl, orphenadrine) are mild antiparkinsonian 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 (e.g. pallidotomy) and stimulation (electrode implants) used in highly selected populations. Older patients often excluded due to high operative risk and rigorous exclusion criteria (e.g. cognitive impairment).
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 PT can be helpful to boost mobility and reduce falls
• OT plays a vital role in aids and adaptations for disability
• SALTs, along with dieticians, can help when swallowing becomes a problem
• Inpatient assessment is rarely helpful, as hospital routines can rarely match home treatment and some patients deteriorate in hospital
• Parkinson’s UK ( http://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 (e.g. sepsis) may miss an oral dose of medication (e.g. 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 the patient is nil by mouth
• When an ileus or other cause makes poor drug absorption likely
► 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 to 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 pre-operative 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; involve pharmacy colleagues
Early action
• Use nasogastric tubes (NGTs) early if swallow is impaired
• Relax nil by mouth rules pre-operatively for Parkinson’s disease drugs
• Use antiemetics (not metoclopramide) when vomiting
Medication
• Use a different preparation, e.g. levodopa dispersible down an NGT, buccal selegiline
• Use an enteral preparation, e.g. apomorphine (s/c delivery) or rotigotine (patch delivery). Advice will be needed from a specialist about doses that are equivalent to their usual medication, but a rough rule of thumb is that 100mg levodopa daily is replaced by a 2mg/24h rotigotine patch
HOW TO . . . Treat challenging symptoms in Parkinson’s disease
See Table 7.3.
Table 7.3 Treatment of challenging symptoms in Parkinson’s disease
Impulse control disorders
• Defined as failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or others
• Tend to occur after the initiation of dopaminergic therapy in those who are susceptible, and abate with dose reduction
Examples include:
• Hypersexuality (see ‘Sexual function’, pp. 530–531)
• Repetitive activities (e.g. arranging objects)
• Dopamine dysregulation syndrome (addictive use of dopaminergic drugs in a Parkinson’s disease patient with other impulse control behaviours)
Further reading
Brennan KA, Genever RW. Managing Parkinson’s disease during surgery. BMJ 2010; 341: 990–3.
National Institute for Health and Care Excellence (2006). Parkinson’s disease in over 20s: diagnosis and management. Clinical guideline CG35. http://www.nice.org.uk/cg35.
Diseases masquerading as Parkinson’s disease
The majority of slow, stiff, or shaky older patients on geriatric wards do not have true Parkinson’s disease (see Table 7.4). As many as one in two diagnoses of Parkinson’s disease made by non-specialists are incorrect. It is important to get the diagnosis right or you will subject patients needlessly to the harmful side effects of medications. Coexistence of more than one syndrome can further complicate the diagnosis.
• Atherosclerotic pseudo-parkinsonism/multi-infarct dementia: due to neurovascular damage—consider in those with stroke/TIA or with atherosclerotic risk factors, e.g. hypertension. Short-stepping, wide-based unstable gait with relative preservation of arm and facial movements (lower body parkinsonism). Head scan may show lacunae or white matter change
• Benign essential tremor: often inherited (autosomal dominant), worse on action (spills tea from teacup), improved by alcohol and β-blockers, may have head nodding or vocal tremor
• Lewy body dementia: Lewy bodies are widely present throughout the cortex, not predominantly in the substantia nigra as with true Parkinson’s disease. Psychiatric symptoms, e.g. visual hallucinations, tend to precede physical ones
• Drug-induced parkinsonism: neuroleptics are the most common cause, but remember that prochlorperazine for dizziness and metoclopramide for nausea are also causes. Some irritable bowel treatments contain neuroleptics
• Other causes: Alzheimer’s disease, hydrocephalus, and even severe polyarthritis can sometimes cause diagnostic confusion. Rare differential diagnoses include Wilson’s disease, Pick’s disease, carbon monoxide poisoning, multiple head injuries (ex-boxers), and post-encephalitis or anoxic brain injury
Parkinson’s plus syndromes
This is a confusing array of rare disorders, including:
• Multisystem atrophy (aka Shy–Drager syndrome, olivopontocerebellar atrophy) with early autonomic failure (incontinence and postural instability), ataxia, parkinsonism, and pyramidal signs. Cognition intact
• Progressive supranuclear palsy (aka Steele–Richardson–Olszewski disease) with up- and downgaze palsy, axial rigidity and falls, dysarthria and dysphagia, and frontal lobe dementia
• Corticobasilar degeneration with asymmetrical ataxia, dementia, and speech/swallow disturbance
Table 7.4 Clues to distinguish Parkinson’s disease clinically
| True Parkinson’s disease | Pseudo-parkinsonism (especially atherosclerotic) | |
| Response to levodopa | ||
| Age of onset | 40–70 | 70+ |
| Tremor | Absent or mild | |
| Progression | Slow progression/long history | Rapid progression |
| Dementia | Only at late stage | Prominent or early |
| Instability/falls | Late | Early and prominent |
| Dysphonia, dysarthria, or dysphagia | Late | Early and prominent |
| Other neurology (pyramidal signs, downgaze palsy, cerebellar signs) | Rare | Common |
Epilepsy
1° epilepsy most commonly presents at around the time of puberty, but the incidence of new fits is actually higher in the over 70s (>100 per 100 000) because of the ↑ amount of 2° epilepsy (caused by, e.g. brain ischaemia, subdural haematomas, brain tumours).
In addition, fits can be precipitated by:
• Metabolic disturbance (e.g. hyponatraemia, hypoglycaemia)
• Infection (at any site, but particularly meningitis/encephalitis)
• Withdrawal from alcohol or drugs such as benzodiazepines
• Wernicke’s encephalopathy (due to thiamine deficiency in malnourished, e.g. alcoholics)
Many of these conditions are more common in older patients who also have a lower fit threshold for any given level of stimulus.
Diagnosis
(See also ‘Syncope and presyncope’, pp. 106–108.)
• An eyewitness account is the most useful diagnostic tool
• Look particularly for post-event confusion/drowsiness which is rare in cardiac syncope
• The classic features of prodrome, tongue-biting, and incontinence are not so useful in distinguishing cardiac from neurological syncope in older patients
• Remember that cerebral hypoperfusion from any cause (e.g. bradycardia) can cause fits, so epilepsy can coexist with other causes of syncope. In these cases, treatment of the 1° syncope/hypoperfusion is more effective than antiepileptics (see ‘HOW TO . . . Distinguish syncope and seizures’, p. 108)
Investigations
• Routine blood screening, CXR, and ECG to look for precipitants and differential diagnoses
• Lactate and creatine kinase (CK) are often elevated after a generalized seizure
• CT scan is vital to exclude a structural lesion
• EEGs can be helpful when positive but very commonly have non-specific changes and low sensitivity, i.e. a normal EEG does not rule out epilepsy
General management
• Ensure the patient is not taking medication that lowers the fit threshold (check the BNF—common examples include tricyclics, ciprofloxacin, tramadol, and phenothiazines. Think about over-the-counter drugs, e.g. Ginkgo biloba, St John’s Wort)
• Correct any metabolic derangement (e.g. glucose, sodium, sepsis)
• Advise about driving restrictions—do not assume they do not drive
• Detect and treat complications, e.g. aspiration, trauma, pressure injuries
Driving regulations and epilepsy
You have a duty to ensure that the patient informs the Driver and Vehicle Licensing Agency (DVLA). If you have reason to believe that the patient has not done so, then your duty to inform the DVLA yourself (after informing the patient of your intention) outweighs confidentiality concerns.
Patients have at least a 6-month ban on driving for a first fit (unless a ‘provoked fit’, e.g. following brain surgery or stroke, when it may be a shorter period—individual decision). They can then reapply for a licence as long as they remain fit-free. Patients must also refrain from driving for 6 months after withdrawing epilepsy medication.
Further information is available at https://www.gov.uk/government/organisations/driver-and-vehicle-licensing-agency.
Epilepsy and stroke
Onset seizures (within a week, most commonly within 24h) occur in 2–5% of strokes. More common with haemorrhages, large cortical strokes, and venous infarction. Consider also alcohol/drug (especially benzodiazepine) withdrawal for early fits. Long-term anticonvulsants not usually prescribed unless fits recur.
After the first week, stroke remains a risk factor for new epilepsy—first year 5% fit, subsequently 1.5% annual incidence. Many such patients develop transient neurological worsening (Todd’s paresis) or permanent worsening without CT evidence of new stroke—in these patients, it is usually worth considering long-term anticonvulsants.
Epilepsy may occur 2° to clinically ‘silent’ cerebral ischaemia, and 3% of patients with stroke have a past history of fits, most occurring in the preceding year. Some epilepsy experts suggest that aspirin is prescribed for new-onset seizures in an elderly patient once structural lesions have been excluded.
Epilepsy: drug treatment
Acute treatment
• Start with benzodiazepines (5–10mg rectal or 2–10mg iv diazepam, or 0.5–2mg lorazepam iv or im)
• If fits continue, consider setting up a loading-dose infusion of phenytoin (use a cardiac monitor) or iv levetiracetam until oral medication can be taken
• Rarely the patient may need intubating and paralysing to stabilize them or to allow an urgent CT scan
Chronic treatment
• Because of side effects and long duration of treatment, most doctors will resist starting anticonvulsants until after a second fit, especially if the diagnosis is unclear or if there is a reversible precipitant. Presence of an underlying structural abnormality or wishing to return to driving may tip the balance in favour of treatment
• The choice of agent shows regional and personal variation
• Most commonly used agents are similarly effective
• Older agents include phenytoin, carbamazepine (both effective but may be sedative), and valproate (better tolerated, but plasma levels are unhelpful in monitoring compliance or side effects)
• Newer agents such as lamotrigine and levetiracetam are ‘cleaner’ and increasingly used as first line
• All anticonvulsants have significant side effects, e.g. sedation, confusion, rash, tremor, and ataxia. Serious liver, blood, and pulmonary side effects can also occur—ongoing monitoring to optimize dose and minimize side effects is necessary
• Many anticonvulsants interact with each other, as well as other drugs, and can ↑ toxicity or reduce effectiveness—if in doubt, consult a pharmacist. Gabapentin and pregabalin are less likely to interact with other medications and can be useful alternatives, especially if their pain-relieving properties are also desirable
• If a known epileptic presents with fits in the context of a new precipitant (e.g. sepsis), then short-term use of clobazam can aid control until the precipitant has been treated
• Avoid abrupt withdrawal of antiepileptics—fits may be provoked
• Partial seizures (e.g. face/arm twitching) are rarely dangerous and often distress bystanders more than the patient, but they can progress to 2° generalized seizures. The same drugs can be employed. Partial seizures often indicate structural lesions and an early CT scan is advisable
• Sometimes a trial of anticonvulsants in patients with recurrent unexplained collapse can be revealing
• Refer to an epilepsy specialist if control is proving difficult and multiple drugs are required
Neuroleptic malignant syndrome
A rare, but important, syndrome in patients taking neuroleptics (e.g. haloperidol, chlorpromazine, risperidone) with a triad of:
• Rhabdomyolysis with 2° renal failure (see ‘Rhabdomyolysis’, p. 507)
► Can be fatal (up to 30%), so early recognition is important.
Diagnosis
May arise at any time during treatment, i.e. the patient may have recently:
• Started (most common) or stopped neuroleptics
• ↑ the dose or been stable on them for a long time
• Added a second drug, e.g. tricyclic antidepressant, lithium
Reintroduction of the offending drug at a later date may not reproduce symptoms. Contributing factors such as intercurrent illness and metabolic derangement may be important in the aetiology.
Clinical features
• The patient looks unwell with fever, severe lead-pipe rigidity, bradykinesia, occasionally tremor, and ↓ conscious level
• Time course: onset usually over 1–3 days, starts with rigidity/altered mental state
• Seizures and abnormal neurological signs can occur
• Autonomic dysfunction causes sweating, tachycardia, and hypertension
• Multiorgan failure can occur; there is leucocytosis, and CK levels may be over 1000IU/L
• Lumbar puncture, CT scan, and EEG are often required to exclude other diagnoses such as CNS infection
► The most common cause of a similar presentation is sepsis in a patient with pre-existing cerebrovascular disease; CK measurement will aid the diagnosis.
Management
Stop all neuroleptics. Cooling using paracetamol, fans, and damp sponging. iv fluids with careful monitoring of electrolytes and renal function. Dantrolene (direct muscle relaxant) can speed recovery. Short-term dialysis is sometimes required. Bromocriptine is used in some cases, although there is limited evidence for efficacy.
Early transfer to the intensive care unit may be wise—death most commonly occurs by hypoventilation/pneumonia or renal failure. There are sometimes persisting neurological sequelae.
Serotonin syndrome
A similar syndrome to neuroleptic malignant syndrome in patients taking serotonin reuptake inhibitors, especially if combined with tramadol, a tricyclic, or an MAOI. Patients tend to be agitated and delirious, rather than unconscious. Gastrointestinal symptoms (diarrhoea/vomiting) occur. Onset may be within 2h; resolution is usually quicker than neuroleptic malignant syndrome.
Motor neuron disease
A progressive idiopathic disease with selective degeneration of motor neurons causing weakness and wasting. There is a variety of manifestations, depending on the site of damage; the most common site for lesions is in the anterior horn cells of the spinal cord (lower motor neuron (LMN)), but the descending motor pathway (upper motor neuron (UMN)) may be affected in the corticospinal tracts, brainstem, and motor cranial nuclei.
► The combination of weakness and fasciculations should always prompt consideration of motor neuron disease (MND).
• Onset rises steeply with age, with a peak incidence in late 50s/early 60s. Very rare before age 40. Overall prevalence of 7 per 100 000, but incidence of 1 per 10 000 at age 65–85
• Underdiagnosed in older patients (confused with cerebrovascular disease, myasthenia, cervical myelopathy, motor neuropathy, syringomyelia, and paraneoplastic syndromes)
• 5% will have a family history (autosomal dominant is the most common but can be recessive or X-linked)
History
• Weakness, cramps, and fatigue in limbs. Weakness usually begins in a focal area and spreads to contiguous muscles; onset in the upper limbs is the most common
• Palatal and vocal cord paralysis can cause stridor, dysarthria, dysphagia, and aspiration pneumonia
• Paresis of respiratory muscles can cause respiratory failure (may present to chest physicians/intensive therapy unit (ITU))
• Intellect, sensation, and continence are usually retained. Some forms associated with frontotemporal dementia (<5%); depression common
Examination
• Look for wasting with fasciculations (LMN), especially in the tongue, shoulders, and legs. ► Fasciculations may be a normal finding in the hands and calves of older people
• Brisk reflexes, clonus, and upgoing plantars (UMN). This is one condition that can cause absent ankle jerks and upgoing plantars
• Atrophy and weakness are less specific signs
• Sensory changes should make you question the diagnosis
Investigations
• CT, MRI, and muscle biopsy are usually normal
• Electromyography (EMG) shows denervation of muscles caused by anterior horn cell degeneration and is diagnostic
Clinical pictures
Diverse presentations and rate of progression, including:
• Amyotrophic lateral sclerosis (ALS) is the most common form—classical picture of mixed UMN and LMN. Term used commonly in the USA
• Progressive pseudobulbar or bulbar palsy—speech and swallow predominantly affected
• 1° lateral sclerosis—UMNs predominantly affected
• Progressive muscular atrophy—LMNs predominantly affected
Treatment
• Riluzole (sodium channel blocker) 50mg twice daily (bd). Prolongs survival by a few months, but not function. Licensed and endorsed by National Institute for Health and Care Excellence (NICE) for ALS only. Expensive and should be initiated by a specialist. Monitor liver function, and check for neutropenia if febrile illness
Supportive
• Chest—antibiotics and PT, tracheostomy, and non-invasive nocturnal ventilation (for diaphragmatic palsy and sleep apnoea)
• Speech—early referral to speech therapy for communication aids
• Nutrition—initially pureed food and thickened fluids. Malnutrition and aspiration are indications to consider artificial feeding (see ‘Nutrition’, pp. 354–355)
• Mobility/independence—OT for wheelchairs and adaptations
• Pain/distress—opiates or benzodiazepines (but beware respiratory suppression)
Other
• This is a devastating diagnosis to give to a patient—the mean life expectancy is 2–5 years. Matters are often worse because there is often a considerable delay between symptoms and a concrete diagnosis being made (sometimes the initial diagnosis may have been incorrect). Emphasize the retention of cognition and aspects of supportive care available. Offer regular follow-up appointments
• Specialist neurology/MND nurses are available in some areas
• Refer to Motor Neurone Disease Association for support
• Consider enduring power of attorney and advance directives (ADs)
Further reading
Motor Neurone Disease Association. http://www.mndassociation.org.
Peripheral neuropathies
Some minor degree of sensory loss in the feet and reduced or absent ankle jerks is so common in older patients (up to 50% of over 85 year olds) that some class this as a normal ageing change, but remember:
• Even mild, asymptomatic neuropathies can contribute to postural instability and falls
• The diagnosis is often missed because of non-specific symptoms and insidious onset with slow progression
Clinical features
• There may be signs of LMN weakness with wasting and loss of reflexes
• Sensory loss often with joint position and vibration loss before touch and pain. This is classically in a ‘glove and stocking’ distribution, rather than dermatomal (see Appendix, ‘Dermatomes’, p. 700)
• Neuralgia-type pain may be present (especially diabetes and alcohol) (see ‘HOW TO . . . Treat neuralgia’, p. 155)
• Autonomic failure and cranial nerve involvement can also occur
• Severe cases may affect respiration
Classification
Try to determine if the signs are focal or generalized and whether they are predominantly sensory or motor because this can help identify the likely underlying pathology. Further classification by pathology (axonal or demyelinating) requires nerve conduction studies or biopsy.
The most common pattern produces widespread symmetrical sensory loss (typically glove and stocking). This may be combined with distal muscle weakness (mixed motor and sensory neuropathy) or sometimes there is a pure motor neuropathy. Where signs are focal, consider mononeuritis multiplex.
Causes
The causes are legion and often multiple in older patients. Idiopathic neuropathies are very common (25% defy diagnosis in most studies). The following list is not exhaustive:
• Paraneoplastic syndromes (e.g. small cell lung cancer)
• Alcoholism (often combined with vitamin deficiency)
• Guillain–Barré syndrome (the most common acute onset)
• Chronic inflammatory demyelinating polyradiculoneuropathy (rare autoimmune motor neuropathy, considered the chronic counterpart of Guillain–Barré)
• Vasculitides (e.g. Wegener’s granulomatosis)
• Drugs (e.g. isoniazid, nitrofurantoin, amiodarone, colchicine)
• Paraproteinaemias and amyloid
Investigations
• Always check B12, glucose, TFTs, serum and urine immunoglobulins, ESR, and CRP before labelling a neuropathy idiopathic
• Look carefully for an occult tumour (e.g. breast examination, iron studies, CXR)
• Nerve conduction studies will confirm nerve damage and distinguish demyelination from axonal damage (which sometimes helps with the differential diagnosis), but they are not always required in straightforward cases
• Further specialist tests include immunology, tumour markers, lumbar puncture, molecular genetics tests, and nerve biopsy
Treatment
The important thing is to identify reversible causes quickly, but even treatable causes rarely respond dramatically—the aim is usually prevention of further deterioration. Chronic inflammatory polyradiculoneuropathy is treated by steroids, plasma exchange, and iv immunoglobulins, but most other chronic neuropathies have no specific treatment. Supportive and symptomatic treatment (e.g. appropriate footwear, analgesia, environmental adaptation) is important.
Guillain–Barré syndrome
This is an acute inflammatory demyelinating polyneuropathy.
• Causes ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk
• It can cause life-threatening complications, particularly if the respiratory muscles are affected or if there is dysfunction of the autonomic nervous system
• The disease is usually triggered by an acute infection
This is a medical emergency which responds to iv immunoglobulins or plasmapheresis. These patients can deteriorate rapidly and should be managed in conjunction with specialist neurology units. Even patients who look well should have their vital capacity measured daily to warn of impending respiratory failure.
► The main hurdle is recognizing the diagnosis.
Subdural haematoma
A condition which is much more common in old age because as the brain shrinks, the veins which lie between it and the skull are much more likely to get torn following trauma (even minor injury). Older people are also more likely to have falls/head injuries and are more frequently on predisposing drugs (e.g. aspirin, warfarin, NOACs). Other risk factors include alcoholism, epilepsy, and haemodialysis.
Features
► Subdurals frequently present with very non-specific symptoms in frail confused patients. A high index of suspicion is required.
• Subdurals can occur acutely (and present within hours of an accident) or more slowly as the classical ‘chronic subdural haematoma’, although this distinction does not help guide management
• A history of head injury occurs in only about half
• Common features include drowsiness and confusion (rarely fluctuating), postural instability, progressive focal neurology (e.g. hemiparesis, unequal pupils), headache, and blurred vision
• Rarely transient neurology (mimicking TIA) or parkinsonism can occur
• Some patients are asymptomatic and large collections can be incidental findings
• Examine for papilloedema, focal neurology, and long tract signs
Diagnosis
• CT head scan—look for crescent-shaped haematoma compressing the sulci (hypodense/black is old blood; hyperdense/white indicates recent bleeding) and midline shift
• All patients who have new UMN signs with confusion and/or drowsiness should be scanned
• It is harder to decide when to scan a confused patient without such signs—most agree it is reasonable to look for other causes of acute confusion before asking for a head scan, as long as the patient is being observed for any change in neurological signs or conscious level
• Have a lower threshold for scanning patients on antiplatelets/anticoagulants and for those who have evidence of falls, particularly facial bruising. MRI can be useful when CT changes are subtle (an isodense phase occurs on CT in transition between hyperdense and hypodense changes) or very small haematomas are suspected
Management
Decisions are usually made in conjunction with the local neurosurgical team (although in practice, only about one-third of patients will end up having surgery).
Stop antiplatelet agents/NOACs, and reverse warfarin therapy if possible.
Observation and supportive care are frequently used in:
• Those with small bleeds who are stable/improving
• Those not fit for transfer/surgery
When conservative management is adopted, record the conscious level (GCS; see Appendix, ‘Glasgow Coma Scale’, p. 710) and any focal neurology at least daily or if there is any change. Any deterioration should prompt a repeat CT scan and reconsideration of surgery.
Burr hole surgery is not complex and is done under local anaesthetic. Recovery after surgery can be dramatic. Complications include re-bleeding and seizures. Use symptoms (especially conscious level), not CT appearance, to decide on surgery. Mortality is around 10%—highest with a depressed conscious level and bilateral haematomas. Those left with residual neurology should receive rehabilitation as in stroke.
Sleep and insomnia
With ↑ age, less sleep is needed (~1h less than young adults); the circadian rhythm is less marked, and sleep becomes more fragmented with greater difficulty getting to sleep. Deep (stages 3 and 4) sleep is reduced, but dreaming sleep/rapid eye movement (REM) is preserved.
Insomnia is a symptom which correlates poorly with observed actual sleep time (i.e. patients who complain of poor sleep may be observed by nurses/family to sleep well, while those who sleep very little do not necessarily complain). It can be very distressing and is associated with ↑ morbidity and mortality. Around 25% of elderly people have chronic insomnia—even higher rates with psychiatric and medical conditions. Insomnia is a particular problem in an unfamiliar noisy ward environment, and doctors are often under considerable pressure to prescribe hypnotics.
Treatment of insomnia
First ensure that underlying causes are looked for and treated:
• Pain at night—consider using analgesics with sedative side effects, e.g. opiates
• Nocturnal urinary frequency, e.g. due to polyuria, peripheral oedema, prostatism
• Comorbidities, e.g. orthopnoea, oesophageal reflux, Parkinson’s disease
• Depression/anxiety—very common and use of an antidepressant will improve sleep much better than a hypnotic
• Drugs—corticosteroids, omeprazole, phenytoin, amiodarone, sulfasalazine, atorvastatin, ramipril, as well as psychiatric drugs, e.g. paroxetine, haloperidol, and chlorpromazine, can cause insomnia. β-blockers and levodopa cause nightmares
The following non-pharmacological interventions (sleep hygiene) can be tried:
• Reduce or stop daytime ‘catnapping’
• Avoid caffeine, heavy meals, and alcohol in the evening (alcohol helps to fall asleep but reduces sleep quality)
• Ensure the environment is dark, quiet, and comfortable
• Relaxation and cognitive behavioural techniques can be useful
• Manage expectations—older people will rarely sleep as much or well as younger people
Drugs
• Benzodiazepines (e.g. temazepam 10mg) are licensed for short-term (<4 weeks) management of insomnia and anxiety. They do work well when used correctly (see ‘HOW TO . . . Use benzodiazepines for insomnia’, p. 175)
• The newer Z-drugs (e.g. zopiclone, zolpidem) are only for insomnia. They have shorter half-lives and fewer side effects (although zopiclone is still a cause of daytime drowsiness). Overall they are probably slightly superior to benzodiazepines, but the same cautions about dependence apply
• Other hypnotics (e.g. chloral hydrate, clomethiazole, antihistamines) can be toxic, especially in overdose, and provide no major advantages
• A new class of drugs that act on melatonin pathways may be beneficial
HOW TO . . . Use benzodiazepines for insomnia
Tolerance develops after only 4 weeks (i.e. benzodiazepines fail to produce a useful sedative effect). However, it takes only this long for dependence to occur. Dependence may be physical (with rebound insomnia, anxiety, or even delirium) and/or psychological (the patient believes they will not be able to sleep without tablets). The shorter the half-life, the greater the withdrawal effects. Benzodiazepine use has been associated with ↑ falls, reduced functional status, road traffic collisions, depression, and memory impairment.
Although awareness of these problems has reduced the number of long-term benzodiazepine users, there is still over-prescribing.
Prevention of dependence
• Do not use benzodiazepines for mild or non-distressing insomnia—try non-pharmacological measures first
• Never prescribe benzodiazepines for >4 weeks
• Never prescribe benzodiazepine medication at discharge from hospital
• All patients/carers should receive warnings about benzodiazepine side effects (especially dependence) and the reason for limiting the course length at the outset
• GPs should limit repeat prescriptions and audit their practice
Treatment of dependence
• Explain and motivate the patient/carers
• In difficult cases, switch to an equivalent dose of diazepam first—long half-life produces milder withdrawal symptoms
• Occasionally acute withdrawal is undertaken by mistake (e.g. drug accidentally not prescribed for a couple of weeks during acute admission with a fractured neck of femur). In these cases, do not automatically restart the benzodiazepines and do explain why to the patient or they will just restart it when they return home
Other sleep disorders
Hypersomnolence
This is excessive daytime sleepiness despite a normal night of sleep. Causes include brain disease (e.g. dementia, stroke), cardiopulmonary disease (e.g. cardiac failure, COPD), obstructive sleep apnoea, hypothyroidism, narcolepsy, and sedative drugs.
Restless legs syndrome
A common (10% older people) unpleasant sensation in the limbs which ↑ with drowsiness and is eradicated by movement. Can be associated with limb jerking during sleep with sleep disturbance. Both symptoms respond to benzodiazepines. Check they are not iron-deficient (replacement can be curative). Treat with dopamine agonists.
Circadian rhythm disorders
Jet lag is the best known, but advanced sleep phase syndrome (sleepiness occurs too early in the evening, but there is early morning wakening) and delayed sleep phase (sleepiness comes too late at night) can occur without such a precipitant. Treat by gradually altering bedtime and bright light therapy when wakefulness is desired.
Sleep apnoea in older patients
Obstructive sleep apnoea and central sleep apnoea are very common in older patients and can contribute to daytime sleepiness, accidents, and heart failure. Unfortunately, periods of apnoea are less likely to be symptomatic than in the young and where symptoms do exist, they are often multifactorial, so diagnosis and compliance with therapy (non-invasive positive pressure ventilation) can be problematic.
REM sleep behaviour disorder
Dream-enacting behaviour during REM sleep, occurring because of a lack of muscle atonia that usually accompanies REM sleep. About half will go on to develop neurological pathology, e.g. Parkinson’s disease, Lewy body disease. Treatment with benzodiazepines may be successful.
Further reading
Harbison J. Sleep disorder in older people. Age Ageing 2002; 31: 6–9.