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Nervous system
Central nervous system abscess
This can occur via direct spread from, for example, mastoiditis or sinusitis, or from a remote region of infection
such as endocarditis or chronic suppurative lung disease.
Haematogenous spread often leads to multiple abscesses.
There is a wide range of possible causative organisms, particularly in the immunocompromised patient, including
aerobic and anaerobic bacteria, fungi, protozoa and helminths. Abscesses are often polymicrobial.
Presentation is most commonly with headache, fever, altered mental status and focal neurological signs.
Features of meningitis or encephalitis may be present
depending on the extent of the inflammation. MRI or
CT scan with contrast enhancement will show a ringenhancing lesion (for the differential diagnosis, see
clinical notes: differential diagnosis of a ring-enhancing
lesion on brain CT/MRI). Treatment will require an
extended course of IV antibiotics, the choice of which
depends on the suspected source and identity of the organism. Surgical aspiration may be required.
CLINICAL NOTES
THE DIFFERENTIAL DIAGNOSIS OF A RINGENHANCING LESION ON BRAIN CT/MRI
• brain abscess
• toxoplasmosis
• tuberculoma
• aspergilloma
• neurocysticercosis
Spinal cord infection
This includes epidural abscesses, viral myelitis and tuberculous myelopathy.
SPINAL CORD DISORDERS
Table32.6 Causes of spinal cord compression
Cause Example
Vertebral (extradural) Collapsed vertebrae, e.g.
Intradural,
extramedullary
Intramedullary Glioma, infection
It is important to note that there is a discrepancy between the level of the root lesion and that of the sensory
level and spastic paraparesis. This arises because the spinal cord is shorter than the spinal column (it ends at the
level of L1–L2 vertebrae in the adult) and, below the cervical spine the nerve roots travel inferiorly before exiting
through the vertebral foramina. For instance, a lesion at the
level of the T10 cord segment may be at the T9 vertebra
level and hence cause T9 root symptoms but a T10 sensory
level. Compression of the cauda equina (the descending
lumbar and sacral nerve roots below the level of the L2 vertebra) causes root pain and lower motor neurone pattern
weakness in the legs, with saddle anaesthesia (numbness
of buttocks and perineum) and sphincter disturbances. If
suspected, MRI or CT is required to show the spinal cord.
This must be done urgently as early intervention may prevent irreversible damage. Neurosurgical opinion should
be sought. Investigations should also include those of the
underlying cause.
Treatment is by decompression, which should be performed as soon as possible to prevent irreversible damage.
Radiotherapy may be useful in malignant disease. If the patient has a known or suspected malignancy, dexamethasone
should be given.
metastatic cancer (bronchus,
breast, thyroid, kidney, prostate),
osteoporosis, myeloma
Spondylosis with disc prolapse
Pott disease (tuberculosis)
Paget disease
Abscess
Reticuloses
Meningioma, haematoma
(subdural, epidural)
Neurofibroma
Spinal cord compression
Spinal cord compression is a medical emergency. The causes
are summarized in Table 32.6. Symptoms include local or
radicular pain, often precipitated by movement or straining,
spastic paraparesis with upper motor neurone signs (hyperreflexia, clonus, Babinski sign) below the level of the lesion
and lower motor neurone signs (hyporeflexia, muscle atrophy) at the level of the lesion, sensory loss with a characteristic ‘sensory level’, autonomic dysfunction (paralytic ileus,
priapism) and sphincter disturbances. Injuries above C3, C4
and C5 lead to phrenic nerve paralysis and diaphragmatic
dysfunction with respiratory compromise.
298
Subacute combined degeneration of the cord
Subacute combined degeneration of the cord is also known
as ‘Lichtheim disease’. This is most commonly due to vitamin B12 deficiency, and refers to patchy demyelination of
the posterior and lateral columns. Vitamin E and copper
deficiencies can result in similar conditions. It is associated
with pernicious anaemia. The onset is usually insidious and
associated with a sensory peripheral neuropathy.
Clinical features include:
• loss of vibration and joint position sense, and positive
Romberg sign: posterior columns;
Peripheral nervous system disorders
3232
• weakness, hypertonia and extensor plantars: lateral
corticospinal tract;
• absent knee jerks and reduced touch sensation:
peripheral neuropathy.
Treatment is with intramuscular vitamin B12 injections.
Syringomyelia and syringobulbia
Syringomyelia is due to a longitudinal cyst (syrinx) usually
in the central cervical spinal cord. As it enlarges it may extend into the dorsal horns and white matter, compressing
the dorsal horn neurones and corticospinal and spinothalamic tracts respectively.
Clinical features are insidious and include:
• Dissociated sensory loss over the upper limbs,
shoulders and trunk in a ‘cape-like’ distribution: loss
of pain and temperature sensation. With progressive
enlargement of the cyst, lower limb light touch,
vibration and proprioception can be affected to involve
the dorsal columns.
• Muscle weakness and wasting, hands are affected first.
The deficit spreads proximally as the syrinx extends.
This reflects involvement of the lower motor neurones
of the dorsal horn.
• Loss of tendon reflexes.
As the syrinx expands, it may lead to spastic paraplegia
with upper motor neurone signs. Insidious loss of normal
sensation may lead to joint destruction (Charcot joints)
or injury. Treatment is by surgical decompression or
aspiration.
If the syrinx extends into the medulla of the brainstem,
this is called ‘syringobulbia’, and may affect cranial nerves,
causing the following symptoms:
• facial pain or sensory loss: cranial nerve V;
• vertigo and nystagmus: cranial nerve VIII;
• facial, palatal or laryngeal palsy: cranial nerves VII, IX,
X and XI;
• wasting of the tongue: cranial nerve XII;
• Horner syndrome: sympathetic tract.
PERIPHERAL NERVOUS SYSTEM
DISORDERS
Peripheral neuropathy
‘Peripheral neuropathy’ is a general term referring to disorders of peripheral nerves; it can be divided into mononeuropathy, mononeuritis multiplex and polyneuropathy. The
causes of these are summarized in Chapter 22. The four
most common causes are diabetes mellitus, malignancy, vitamin B12 deficiency and drugs (notably alcohol). Treatment
is aimed at the underlying disorder. Some specific peripheral nerve syndromes are considered here.
Guillain–Barré syndrome
This is an acute immune-mediated condition with several
subtypes, the most common of which is acute inflammatory
demyelinating polyneuropathy. Guillain–Barré syndrome
(GBS) affects motor nerves more than sensory nerves.
Seventy-five percent of patients have a history of an infective illness days or weeks before the condition develops.
Linked pathogens include Campylobacter spp., cytomegalovirus, Epstein–Barr virus, and HIV.
Clinical features
Clinically, there is ascending progressive, relatively symmetrical weakness accompanied by paraesthesia, hyporeflexia
and numbness. Symptoms most commonly start in the lower
limbs and progressively worsen to involve the upper limbs,
trunk and respiratory and cranial nerves. In 10% of patients,
arms or facial muscles are the first to be affected, and in the
Miller Fisher subtype there is ophthalmoplegia and ataxia.
Complications of GBS include respiratory failure, cardiac
arrhythmias due to autonomic dysfunction and aspiration
due to bulbar palsy. Because of immobility, patients are at
high risk of deep vein thrombosis and pulmonary embolism.
Most patients with GBS start to improve within 1month.
A small proportion of patients will continue to progress or
experience relapses; if this continues for more than 8weeks,
the illness is termed chronic inflammatory demyelinating
polyneuropathy.
Investigations
The CSF shows a high protein concentration (up to 10 g/L)
and a normal cell count. Nerve conduction studies are abnormal in most patients. Forced vital capacity helps predict
respiratory outcomes. In addition, the patient's swallowing
should be monitored closely as should the postural drop
in blood pressure (as an indicator of autonomic function).
ECG can reveal conduction abnormalities.
Management
Supportive measures include nutritional support, analgesia,
skin care and thromboprophylaxis. Chest physiotherapy
lowers the risk of pneumonia. Mechanical ventilation may
be necessary. No definitive curative treatment exists. IV administration of immunoglobulin and plasma exchange have
been shown to improve outcomes, and are recommended
for patients presenting up to 4 weeks after the onset of
symptoms. Steroids alone are of no benefit.
Around 5% of severely affected patients will die in intensive care. Around 90% of patients have a good recovery.
Entrapment/compression neuropathies
These are extremely common syndromes causing
mononeuropathy with neurological symptoms and signs
299
Nervous system
in the distribution of a single peripheral nerve. The injury
to the nerve may be transient, changing with position, but
with chronicity, demyelination and axonal degeneration
may occur.
The following are some of the most frequently encoun-
tered conditions:
• carpal tunnel syndrome: compression of the median nerve
as it passes through the carpal tunnel at the wrist, causing
numbness, paraesthesiae and weakness of the hand;
• radial nerve palsy: compression of the radial nerve,
frequently at the spiral groove in the upper arm,
causing weakness of the wrist and finger extensors,
with numbness of the dorsum of the hand and forearm
('Saturday night palsy', so called after intoxicated
patients who fall asleep and lie on their upper arm for
prolonged periods);
• meralgia paraesthetica: entrapment of the lateral
cutaneous nerve of the thigh as it passes under the
inguinal ligament, causing numbness over the lateral
aspect of the thigh.
NEUROMUSCULAR DISORDERS
Muscle disorders
For more on muscle disorders, see polymyositis and dermatomyositis in Chapter34.
Myotonic dystrophy (myotonia dystrophica)
This is an autosomal dominant condition characterized by
myotonia: the inability of the muscles to relax normally after contraction. The peak onset is between the ages of 20
and 30years, and the incidence in the United Kingdom is
approximately 5 in 100,000. There is muscle wasting and
weakness. Myotonia of the facial muscles results in ptosis, a
wry smile or ‘sneer’ and a ‘hang-dog’ expression due to the
thin face and lax jaw muscles.
Other associated features include frontal baldness, cataracts, testicular or ovarian atrophy, cardiomyopathy with
conduction disturbances, mental impairment and endocrine
dysfunction, including diabetes. Reflexes are lost. The myotonia is often revealed by shaking the patient's hand (slow to release grip) or by asking patients to repetitively open and close
their eyes or fists. It may be elicited by percussion of the thenar
eminence—the induced depression is slow to fill (‘percussion
myotonia’). It increases with fatigue, cold and stress. Diagnosis
is by genetic testing. There is no curative treatment. Myotonia
may be relieved with procainamide or phenytoin.
Muscular dystrophy
Muscular dystrophy (MD) is a group of genetically determined diseases characterized by progressive degeneration
and weakness of certain muscle groups.
Duchenne and Becker muscular dystrophy (pseudohypertrophic)
These are the commonest types of MD, and are X-linked recessive progressive disorders. Both involve mutations of the
dystrophin gene. Duchenne MD presents in early childhood
with clumsiness in walking and difficulty climbing stairs.
Examination reveals a lordotic posture and ‘waddling’ gait
due to proximal muscle weakness. The calves are hypertrophied. When rising from the floor, patients may need to
use their hands to bring themselves into an upright position (Gower sign). Investigations show a markedly raised
creatine kinase concentration. Electromyography and muscle biopsy show characteristic changes. Cardiomyopathy is
common. Death usually occurs before the age of 20years
from intercurrent illnesses (e.g. chest infection). There is
no specific treatment. Becker MD is less severe, with onset
usually in the teenage years and survival beyond the third
decade.
Facioscapulohumeral dystrophy (Landouzy– Dejerine syndrome)
This is autosomal dominant. The onset is around puberty
with wasting and weakness of the upper limb girdle and
face. Life expectancy is usually normal.
Limb girdle dystrophy
This describes a group of disorders affecting predominantly
proximal muscles. Most are autosomal recessive, and onset
in the most common types is in childhood. The condition is
progressive, with death in middle age. There may be cardiac
involvement.
Neuromuscular junction disorders
Myasthenia gravis
This is an autoimmune disease where skeletal muscle weakness is caused by a reduction in the number of functional
postsynaptic acetylcholine receptors, and their eventual
destruction. Autoantibodies detectable in most patients
include antibody to acetylcholine receptor and antibody to
muscle-specific receptor tyrosine kinase. Myasthenia gravis
is associated with thymoma and thymus hyperplasia, hyperthyroidism, rheumatoid arthritis and SLE. The UK incidence is around 15 per 100,000.
Clinical features
In younger patients (<50years) it is more common in females and is associated with other autoimmune conditions.
There is painless muscle weakness, which worsens on repetitive contraction and fluctuates over the day. Most patients
present with extraocular muscle weakness causing ptosis
and diplopia. The facial and bulbar muscles are commonly
affected, causing the 'myasthenic snarl' on smiling, dysarthria with a ‘nasal’ sounding voice and dysphagia. Proximal
muscles and upper limbs are more often affected than distal muscles and lower limbs. Reflexes are usually normal.
In 15% of patients, the disease remains limited to the eyes.
300
Miscellaneous disorders
3232
Myasthenic crisis is a rare complication with rapidly worsening weakness often precipitated by infection or medication. Respiratory weakness is the concern in this case, and
the patient may require mechanical ventilation.
Investigations
Diagnosis is mostly clinical. Anti-acetylcholine receptor
antibody can be measured and, if this is negative, musclespecific receptor tyrosine kinase antibody should be measured in the serum. All patients should have thyroid function
tests and a thymus scan. Neurophysiological tests can be
conducted to demonstrate poor muscle responsiveness.
Management
Symptomatic control is with a long-acting anticholinesterase (e.g. pyridostigmine or neostigmine). The dose is
slowly titrated against muscle power. Side effects include
nausea, vomiting, increased salivation, diarrhoea and abdominal cramps. Cholinergic crisis can occur, and is similar
in presentation to myasthenic crisis.
Acetylcholinesterase inhibitors are usually combined
with immunosuppression. Corticosteroids on alternate days
may achieve remission. If there is no remission and weakness is severe, azathioprine, methotrexate, tacrolimus or rituximab may be helpful. The condition is usually relapsing
or slowly progressive, and respiratory muscle involvement
can lead to death. Thymectomy should be considered even
in patients without a thymoma.
Lambert–Eaton myasthenic syndrome
This is an autoimmune condition but may be paraneoplastic; around 50% of cases are associated with small cell
lung cancer. Antibodies to the presynaptic P/Q-subtype
voltage-gated calcium channels are present. This leads to
impaired presynaptic release of acetylcholine.
Here, as opposed to in myasthenia gravis, weakness
diminishes with exertion. Slowly progressive weakness is
typical, particularly affecting the lower limbs. Autonomic involvement and hyporeflexia are characteristic. Symptomatic
therapy with acetylcholinesterase inhibitors or guanidine
is possible. Significant increase in muscle strength can be
achieved with 3,4-diaminopyridine. IV immunoglobulin or
plasma exchange can also be used. Immunosuppressants are
used in severe cases. Regular chest X-rays are important to
investigate patients for signs of malignancy; the neurological symptoms may predate cancer detection by months or
even years.
MISCELLANEOUS DISORDERS
Motor neurone disease
This is a disease involving progressive degeneration of the
motor cortex, pyramidal and corticospinal tracts, lower cranial nerve nuclei (hence the external ocular movements are
normal) and anterior horn cells of the spinal cord. Both upper and lower motor neurones can be affected. Sensation is
preserved. Presentation differs. Patients can report stiffness,
cramps, muscle weakness and wasting. As the condition
progresses, muscular weakness becomes more pronounced,
respiratory compromise may occur and swallowing and
communication are affected; frontotemporal dementia occurs in around 10%–15% of patients.
Motor neurone disease (MND) is slightly more common
in men. Peak incidence is between the age of 55years and
the age of 79years, but people at any age can be affected.
The cause is unknown. Familial forms account for 5%–10%
of cases and are usually due to mutations in the superoxide dismutase 1 gene (SOD1), although mutations of many
other genes have been implicated in the pathogenesis of
both the familial forms and the sporadic forms.
Clinically there are four main patterns of disease:
• Amyotrophic lateral sclerosis (ALS): the most common
type of MND. Combined lower motor neurone (LMN)
wasting and upper motor neurone (UMN) spasticity
and hyperreflexia. Weakness usually starts in the legs
and spreads to the arms.
• Progressive muscular atrophy: anterior horn cell
involvement, leading to lower motor neurone weakness
and wasting and fasciculation of distal muscles, which
spreads proximally.
• Progressive bulbar palsy: LMN weakness and wasting
of the tongue and pharynx, leading to dysarthria and
dysphagia. UMN features such as stiff tongue, spastic
speech and brisk jaw jerk are also usually present.
Involvement of descending motor neurone pathways
which arise in the cerebral cortex and brainstem (long
tracts), is common.
• Primary lateral sclerosis: disease limited to upper
motor neurones; LMN signs may develop later in the
disease. Progression is slower than for ALS.
Combinations of the afore mentioned conditions may
occur.
Management
Treatment is symptomatic. The aim is to help the patient
with activities of daily living and to adequately manage symptoms. Quinine can be used for muscle cramps.
Baclofen is an alternative and it can also help with muscle
stiffness, spasticity and increased tone. Opiates should be
considered for joint pains and distress. Physiotherapy, occupational therapy and speech and language therapy teams
should be involved. Difficult decisions regarding nasogastric or percutaneous endoscopic gastrostomy feeding and
artificial ventilation may arise. These interventions may
prolong life but also the process of dying. Riluzole, an antiglutamate drug, is licensed in MND and offers a small increase in the length of life. Other agents are used in trials.
Death usually occurs 2–3years after diagnosis; 25% survive
to 5years and 5%–10% survive to 10years.
301
Nervous system
Smoothing ou
of forehead
Eyebrow droo
Loss of
nasolabial
fold
Inability to clos
eye full
Dif
cheeks as cannot
seal lips
when patient smiles
Horner syndrome
This describes the combination of miosis (pupillary constriction), partial ptosis and ipsilateral loss of sweating (anhidrosis) caused by interruption of the sympathetic nerve
supply to the face. The sympathetic nerves may be disrupted
anywhere along their course:
• brainstem: demyelination, vascular disease;
• cervical cord: syringomyelia;
• thoracic outlet: Pancoast tumour;
• neck (postganglionic): carotid artery aneurysm or
dissection, tumours.
Bulbar and pseudobulbar palsy
These two conditions result from disruption of lower cranial nerve motor function, affecting the tongue, muscles of
chewing/swallowing (therefore causing an increased risk of
aspiration) and facial muscles.
Bulbar palsy (‘bulbar’ refers to the medulla) is an LMN
syndrome affecting cranial nerves VII–XII. Clinical features
include flaccid, fasciculating tongue, normal or absent jaw
jerk and quiet nasal speech. It is caused by diphtheria, motor neurone disease, Guillain–Barré syndrome, poliomyelitis, cerebrovascular event of the brainstem, syringobulbia
and brainstem tumours.
‘Pseudobulbar palsy’ refers to bilateral upper motor neurone lesions affecting the brainstem motor nuclei (corticobulbar tracts). The tongue is spastic or paralysed, jaw jerk
is increased, speech sounds like ‘Donald Duck’ and there
is emotional lability. Pseudobulbar palsy is more common
and is usually due to cerebrovascular events (e.g. bilateral
internal capsule strokes). Other causes include MS, MND,
high brainstem tumours and neurosyphilis.
Bell palsy
This is an idiopathic unilateral lower motor neurone palsy
of cranial nerve VII. Other causes must be excluded (see
t
p
e
y
ficulty puffing out
Drooping of corner of mouth
— particularly evident
Fig.32.4 Bell palsy.
Chapter2). It is thought that viral infections account for
most cases.
Rapid onset of facial weakness occurs and may be accompanied by pain below the ear. There may be loss of taste
in the anterior two-thirds of the tongue. The characteristic physical signs are described in Chapter2 and shown in
Fig.32.4. Bell palsy specifically due to varicella zoster infec-
tion is termed ‘Ramsay Hunt syndrome’.
Most patients recover fully within a few weeks. Some have
axonal degeneration and recovery is delayed and may be incomplete. Occasionally, aberrant reconnections are formed (e.g. eating may stimulate unilateral lacrimation—'crocodile tears').
Steroids are effective in treating the condition if given
within 72 hours. The role of antiviral drugs remains
controversial. The eye must be protected when closure is
incomplete: patches and artificial tears are useful.
302
Chapter Summary
• Subarahnoid haemorrhage classically presents with sudden onset severe headache.
• Patients with an extradural haematoma will usually have a reduced level of
consciousness, followed by a lucid interval.
• Migraine can be present with features similar to a stroke.
• Carbamazepine is used as first line treatment for trigeminal neuralgia.
• Status epilepticus is a medical emergency and should be treated immediately.
Lorazepam or other benzodiazepines are used as first line treatment.
• Multiple sclerosis is an autoimmune, inflammatory, demyelinating condition.
• Pneumococcus, H. influenzae, and type b meningococcus are the most common causes
of meningitis in adults in the UK.
• Listeria is a cause of meningitis in immunocompromised and elderly patients.
• Myasthenia gravis is an autoimmune condition where acetylcholine receptors are affected.
Further reading
3232
FURTHER READING
NICE 2017, Stroke and transient ischaemic attack in over 16s: diag-
nosis and initial management.
NICE 2017, Stroke and TIA management, scenarios.
NICE 2016, Cardiovascular disease: risk assessment and reduction,
including lipid modification.
NICE 2016, Migraine management, scenarios.
NICE 2014, Trigeminal neuralgia, scenario: management.
NICE 2016, Epilepsy: diagnosis and management.
NICE 2006, Parkinson’s disease in over 20s: diagnosis and management.
NICE 2017, Parkinson’s disease with motor fluctuations: safinamide.
NICE 2014, Multiple sclerosis in adults: management.
NICE 2015, Meningitis (bacterial) and meningococcal septicaemia
in under 16s: recognition, diagnosis and management.
NICE 2016, Motor neurone disease: assessment and management.
Intercollegiate Stroke Working Party, 2016, National clinical guide-
line for stroke, 5th edition. London: Royal College of Physicians.
International League Against Epilepsy website: http://www.ilae.org
https://www.gov.uk/epilepsy-and-driving.
http://www.cancerresearchuk.org/health-professional/cancer-
statistics/statistics-by-cancer-type/brain-other-cns-and-
intracranial-tumours.
Polman, C.H., Reingold S.C., Banwell B., etal. (2011) Diagnostic
criteria for multiple sclerosis: 2010 revisions to the McDonald
criteria. Annals of Neurology 69: 292–302.
303
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Metabolic and endocrine
DIABETES MELLITUS
Diabetes mellitus is a persisting state of hyperglycaemia due
to diminished availability or effectiveness of insulin. There
were 171 million people in the world with diabetes in 2000,
and there are an estimated 422 million currently globally,
according to the latest World Health Organization (WHO)
data from 2016 (90% being people with type 2 diabetes),
and this is projected to almost double by 2030. In the United
Kingdom, it is estimated that around 4.5% of the population
have diabetes. The rising tide of obesity is responsible for
much of this.
The WHO criteria used for the diagnosis of diabetes
mellitus are shown in Table33.1. In addition to these tests,
diabetes can be diagnosed on a random blood sample if glucose level is above 11.1 mmol/L and symptoms are present.
‘Impaired fasting glycaemia’ and ‘impaired glucose tolerance’ refer to fasting (no intake of calories for 8 hours) and
postprandial abnormalities of glucose metabolism, respectively; the terms are not interchangeable. In both cases, patients have an elevated risk of progression to frank diabetes
and increased risk of macrovascular disease (see later).
CLINICAL NOTES
A glycated haemoglobin level of greater than
48 mmol/mol can also be used to diagnose type 2
diabetes. This has the advantage of not requiring
a fasting blood sample. It cannot be used to
diagnose type 1 diabetes, and is not reliable in the
acutely unwell, new presentations of diabetes, or
in the context of altered erythropoiesis (e.g. iron
deficiency, vitamin B12 deficiency, renal or liver
disease).
disorders
33
Aetiology and Pathophysiology
Type 1 diabetes mellitus usually presents in childhood, with
a peak age of incidence of 10–15years, although it can occur at any age. The signs and symptoms develop quickly
over days to weeks. Type 1 diabetes is due to autoantibodies directed against the insulin-producing beta cells of the
pancreatic islets of Langerhans, causing a low concentration
of circulating insulin. These patients always require insulin
replacement therapy, and there is an association with other
autoimmune diseases.
Patients with type 2 diabetes mellitus are usually older
and overweight, and the onset is more insidious. Type 2
diabetes is due to a combination of reduced sensitivity of
peripheral tissues to circulating insulin (insulin resistance)
and failure of the beta cells to produce enough insulin to
overcome this resistance. Patients may require insulin if
hyperglycaemia persists despite maximal doses of oral hypoglycaemic agents, or in times of physiological stress such
as severe infections or after myocardial infarction. There is
approximately 80% concordance between identical twins
for type 2 diabetes mellitus, suggesting that inherited factors
have a significant role. Type 2 diabetes is increasingly seen
in children, and may be linked with rising levels of childhood obesity. A very small proportion of patients with type
2 diabetes have a familial autosomal dominant form and
present at a young age. This was previously called ‘maturity
onset diabetes of the young’ (MODY) but is now classified
according to the genetic defect. Secondary diabetes mellitus
may be caused by:
• drugs (e.g. steroids);
• pregnancy (gestational diabetes): patients develop
impaired glucose tolerance or frank diabetes during
pregnancy;
• pancreatic disease (e.g. pancreatectomy, carcinoma
of the pancreas, pancreatitis, cystic fibrosis,
haemochromatosis);
• endocrine causes (e.g. Cushing syndrome, acromegaly,
phaeochromocytoma).
Table33.1 World Health Organization (2006) criteria for the diagnosis of diabetes and intermediate hyperglycaemia
Fasting plasma glucose (mmol/L) 2-h plasma glucosea (mmol/L)
Diabetes ≥7.0 or >11.1
Impaired glucose tolerance <7.0 and ≥7.8 and <11.1
Impaired fasting glucose 6.1–6.9 and (if
a
Venous plasma glucose 2 hours after ingestion of an oral 75-g glucose load.
measured)
<7.8
305
Metabolic and endocrine disorders
CLINICAL NOTES
In cases where it is difficult to differentiate between
type 1 and type 2 diabetes, test for the presence
of antibodies to pancreatic islet cells, glutamic acid
decarboxylase or insulin. Glycated haemoglobin
level is often measured at presentation, and may
be useful in distinguishing patients with diabetes
from those with transient hyperglycaemia.
Features characteristic of
type 1
— Ketones on breath*
— Hyperventilation*
Features common to
type 1 and type 2
Brain
— Tiredness
— Impaired consciousness*†
— Impaired visual activity
Mouth
— Polydipsia (thirst)
— Vomiting*
Heart/cardiovascular system
— Tachycardia*†
— Hypotension*†
Clinical features
Fig.33.1 demonstrates some of the differences in presenta-
tion between type 1 and type 2 diabetes. Diabetes may be
asymptomatic and discovered on routine screening, where
elevated levels of glucose are found in the blood or urine,
but type 2 diabetes remains undiagnosed in approximately
half of all people with this condition. Patients may present
with nonspecific symptoms such as weight loss and lethargy
(mainly seen in type 1 diabetes), and they are more prone to
infection (e.g. thrush, cellulitis, fungal infections). Polyuria
and polydipsia are characteristic and relate to the osmotic
Features characteristic of
type 2
Blood
— Hyperglycaemia*
— No ketoacidosis
— Islet cell
antibodies not
present
Minimal
weight loss
Urine
— No trace
of ketonuria
Blood
— Hyperglycaemia*
— ± ketoacidosis*
— Islet cell
antibodies
often present
at presentation
Weight loss prior
to presentation
Urine
— Ketonuria*
Type 1 diabetes mellitus
• Patients usually thin
• Usually present with a short history of acute symptoms
• Treat with insulin
Muscles
— Weakness and wasting
Kidneys
— Polyuria
— Prone to infection
Skin
— Prone to infections
(e.g. pruritus vulvae,
boils)
* Features of DKA
† Features of HHS
Type 2 diabetes mellitus
• Patients usually overweight (85% obese)
• Usually present with a longer history, with slowly progressing
symptoms or with chronic complications
• May be asymptomatic, or have less severe but slowly progressing
symptoms similar to type I diabetes, e.g. increasing tiredness
• Many cases are discovered only by routine testing
• Treat with diet and oral hypoglycaemic agents initially (may need
insulin subsequently)
Fig.33.1 Acute symptoms and signs of diabetes mellitus (types 1 and 2). DKA, Diabetic ketoacidosis; HHS, Hyperosmolar
hyperglycaemic state.
306
Diabetes mellitus
Brain
Penis
– Impotence
— Neuropathy
3333
diuresis caused by the filtered glucose load in the nephrons
overcoming their ability to reabsorb it.
A significant proportion of patients present for the first
time with a diabetic emergency: diabetic ketoacidosis (DKA)
in the case of type 1 diabetes or, more rarely, hyperosmolar
hyperglycaemic state (HHS), in the case of type 2 diabetes.
Some patients, particularly people whose type 2 diabetes
has an insidious onset, may present with chronic complications of their diabetes. Fig.33.1 summarizes the characteristic presenting features in diabetes mellitus.
The chronic complications of diabetes are summarized
in Fig.33.2. They can be considered in two broad groups:
macrovascular and microvascular. ‘Macrovascular’ refers to
complications related to larger blood vessels (e.g. coronary
artery, cerebrovascular and peripheral vascular disease).
‘Microvascular’ refers to complications related to smaller
blood vessels (e.g. diabetic retinopathy, nephropathy and
— Cerebrovascular disease/strokes
Eyes
— Retinopathy and cataracts
(diabetes is the commonest
cause of blindness under
the age of 60 years)
neuropathy). Some complications will arise because of both
macrovascular and microvascular disease.
Macrovascular disease
This is a cause of significant morbidity and mortality
among people with diabetes. A person with diabetes has a
risk of myocardial infarction equivalent to that of a nondiabetic person who has already had one previous infarction.
Therefore it is of paramount importance to assess and address all cardiovascular risk factors when you are treating
patients with diabetes (see later).
Microvascular disease
Diabetic retinopathy
Retinopathy occurs in virtually all patients with type 1 diabetes, and maculopathy occurs in up to 20% of patients.
Patients with type 2 diabetes often have a degree of retinopathy at presentation. The stages of diabetic retinopathy are
shown in Chapter2 (see Table2.17). Patients with maculopathy and preproliferative changes must be referred to
an ophthalmologist; those with proliferative retinopathy
require urgent referral for laser therapy.
People with diabetes are also at elevated risk of early
cataract formation. Rubeosis iridis is a late complication related to new vessel formation on the iris, and may result in
glaucoma.
Heart
— Coronary heart disease,
myocardial infarction
Blood pressure
— Tendency to get
hypertension
Kidneys
— Nephropathy leads to
renal failure
— Prone to infections
Limbs
— Ischaemia, neuropathy
leads to dry, anaesthetic
skin
Skin
— Prone to skin infections
Blood vessels
— Peripheral vascular disease
causes claudication in legs,
gangrene in feet
Feet
— Prone to ulcers and gangrene
Diabetic nephropathy
The first sign of renal involvement is microalbuminuria
(30–300 mg albumin in 24 hours). A negative dipstick test
does not exclude microalbuminuria, and therefore more
sensitive tests must be used to screen people with diabetes: use the albumin-to-creatinine ratio from a spot urine
sample. Microalbuminuria affects 20%–40% of people with
diabetes 10–15 years after diagnosis. These patients can
progress to macroalbuminuria/clinical nephropathy (albumin excretion greater than 300 mg in 24 hours). Diabetic
nephropathy can be a cause of nephrotic syndrome (see
Chapter30) and is the leading cause of end-stage renal fail-
ure in the United Kingdom.
CLINICAL NOTES
Diabetic nephropathy is almost always associated
with the presence of retinopathy, and its absence
should prompt a search for an alternative renal
diagnosis.
The pathological hallmark of diabetic nephropathy
on histology from a renal biopsy sample
is the Kimmelstiel–Wilson lesion (nodular
glomerulosclerosis).
Fig.33.2 Chronic complications of diabetes mellitus.
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