Peripheral Neuropathy Flashcards
Cryoglobulinaemic peripheral neuropathy
Cryoglobulinaemia is the presence of circulating proteins which precipitate in the cold. It is commonly associated with hepatitis C infection. Through a variety of mechanisms, cryoglobulins cause a small-vessel vasculitis which may result in an axonal peripheral neuropathy. This may be sensorimotor, or purely sensory.
Example Question:
A 32 year-old man presents to the neurology clinic with burning pains in both feet, which has progressed over the last year.
His past medical history includes hepatitis C, and last year he was commenced on treatment with pegylated interferon and ribavirin.
On examination, power is normal throughout. Reflexes are present normally in the arms but only with reinforcement in the knees, and absent in the ankles. Sensation to pin-prick, joint position, and vibration is absent up to the knees.
Nerve conduction studies show reduction in the amplitude of lower limb sensory action potentials, in a length-dependent fashion. Conduction velocities are relatively preserved. Motor studies are normal.
What is the most likely cause of this mans pain?
Diabetic small-fibre neuropathy Fabrys disease Drug-induced peripheral neuropathy > Cryoglobulinaemic peripheral neuropathy Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
Small-fibre Neuropathy (Diabetic)
Small-fibre neuropathy typically presents with pain and loss of temperature sensation, with relative preservation of other sensory modalities and muscle strength. This form of neuropathy is not detectable on conventional nerve conduction studies, which can only investigate large fibres. Diabetes is a common cause and should be excluded in any patient with a painful peripheral neuropathy.
Fabry’s Disease
Fabrys disease is an X-linked lysosomal storage disorder which causes a painful peripheral neuropathy, due to deposition of glycosphingolipids within small sensory fibres. Nerve conduction studies are typically normal as large fibres are unaffected.
Drug-induced Peripheral Neuropathy
Drugs such as metronidazole, isoniazid, and cytotoxic chemotherapy agents are common causes of peripheral neuropathy.
DRUGS CAUSING PERIPHERAL NEUROPATHY Drugs causing a peripheral neuropathy: - Antibiotics: nitrofurantoin, metronidazole - Amiodarone - Isoniazid - Vincristine - Phenytoin - Alcohol - Heavy metals e.g. Thallium
NB Nitrofurantoin can cause a peripheral neuropathy, especially in patients with pre-existing renal impairment.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
CIDP typically presents with prominent motor involvement, often affecting proximal as well as distal muscles. Sensory involvement is common, often affecting joint position and vibration sense, which are mediated by large myelinated fibres. On nerve conduction studies the typical finding is conduction slowing reflecting demyelination, rather than reduced amplitudes which suggest axonal loss
Guillain-Barre Syndrome
Guillain-Barre syndrome describes an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni).
Guillain-Barre Syndrome - Mx
Management
- plasma exchange
- IV immunoglobulins (IVIG): as effective as plasma exchange. No benefit in combining both treatments. IVIG may be easier to administer and tends to have fewer side-effects
Immunomodulatory treatment has been proven to hasten recovery in GBS. Intravenous immunoglobulin (IVIG) and plasma exchange have proved equally effective, however, IVIG is often the initial treatment for practical reasons.
Corticosteroids (oral and intravenous) have not been found to have a clinical benefit in GBS. Consequently, this class of drugs is not currently employed in the treatment of the syndrome.
Immunosuppressants have not been shown to be beneficial
- FVC regularly to monitor respiratory function
Charcot’s Joint (Sensory neuropathy)
Charcot joint
A Charcot joint is also commonly referred to as a neuropathic joint. It describes a joint which has become badly disrupted and damaged secondary to a loss of sensation. In years gone by they were most commonly caused by neuropathy secondary to syphilis (tabes dorsalis) but are now most commonly seen in diabetics.
Features
Charcot joints are typically a lost less painful than would be expected given the degree of joint disruption due to the sensory neuropathy. However, 75% of patients report some degree of pain
the joint is typically swollen, red and warm
Charcot Joint - Example Question
An 85-year-old woman presents with a long history of poorly controlled type 2 diabetes mellitus presents to her GP complaining of a swollen right foot. She describes it as a ‘gammy’ foot and says she is always tripping over it. The pain is described as being 2 out of 10. The patient also describes reduced sensation up to her ankles.
On examination she has reduced sensation in both feet. The right midfoot is swollen, warm and slightly erythematous but there is no ulcer present. The dorsalis pedis pulse is difficult to feel on the right hand side.
An x-ray is requested:
SEE PASSMED IMAGE CHARCOT JOINT
What is the most likely diagnosis?
Septic arthritis of the 1st metatarsophalangeal joint Osteomyelitis > Charcot joint Critical ischaemia of the right foot secondary to peripheral arterial disease Gout
The x-ray shows extensive bone remodeling / fragmentation involving the midfoot. In combination with the presence of a swollen, red, warm joint in a patient with a history of poorly controlled diabetes is highly suggestive of a Charcot’s joint.
The x-ray findings are not consistent with osteomyelitis and questions would often give other clues such as an overlying ulcer, which is not present in this case.
HSMN
Hereditary sensorimotor neuropathy (HSMN) is a relatively new term which encompasses Charcot-Marie-Tooth disease (also known as peroneal muscular atrophy). Over 7 types have been characterised - however only 2 are common to clinical practice
HSMN type I: primarily due to demyelinating pathology
HSMN type II: primarily due to axonal pathology
HSMN Type I
HSMN type I
autosomal dominant
due to defect in PMP-22 gene (which codes for myelin)
features often start at puberty
motor symptoms predominate
distal muscle wasting, pes cavus, clawed toes
foot drop, leg weakness often first features
HSMN - Example Question
A 55-year-old female presents with 3 weeks of bilateral tingling sensation in her medial one and half digits at night. She has noted a clawing of her 4th and 5th digits and she is particularly concerned by the cosmetic elements. She also complains of a left sided foot drop present over the past 8 months. Her past medical history includes type 2 diabetes mellitus, for which she take metformin 850mg TDS and she admits to occasional poor compliance. Her last HbA1c was 7 mmol/l. She has also had multiple admissions for surgery to her feet at childhood but she is unaware of further details. She was adopted and is unaware of her birth family history. On examination, she clinically has a left common peroneal palsy with bilateral thin calves, and loss of sensation in bilateral ulnar nerve territories. What is the unifying diagnosis for her presenting paraesthesia and foot drop?
> Hereditary neuropathy with liability to pressure palsies Diabetic neuropathy Chronic inflammation demyelinating polyneuropathy (CIDP) Systemic lupus erythematosus (SLE) Sarcoidosis
The patient has thin calves and previous foot deformities requiring surgery, suggestive of Charcot-Marie-Tooth disease or hereditary motor sensory neuropathy (HSMN), a disorder caused by deletion in the PMP22 gene, the same gene mutation responsible for hereditary neuropathy with liability to pressure palsies. Common peroneal nerve is the most commonly affected nerve (36%) followed by the ulnar nerve (28%). Diagnosis is confirmed by genetic testing
Drugs causing Peripheral Neuropathy
Drugs causing a peripheral neuropathy antibiotics: nitrofurantoin, metronidazole amiodarone isoniazid vincristine
Drug-induced Peripheral Neuropathy - Example Question
A 45 year old Bangladeshi male presents with a 6 month history of bilateral reduced sensation on the tips of both his feet, which has gradually progressed on both legs to his low shins. His past medical history include type 2 diabetes, diagnosed 7 years ago and reports good medication compliance with metformin 500mg BD alone, with a HbA1c at 6.5mmol/l two weeks ago. He is also currently on his ninth month of anti-tuberculosis treatment, having initially presented with a chronic cough, night sweats and weight loss. An induced sputum subsequently cultured positive for acid fast bacilli. He did not bring in his medications but remembers being told they are ‘the standard four then two drugs’. He takes no other medications and has no known drug allergies. On examination, tone, power and gait of his lower limbs are unremarkable. He demonstrates reduced sensation to light touch to his left lower-shin and right mid-shin. Ankle jerks are absent bilaterally, plantars are downgoing bilaterally. What is the most likely diagnosis?
Guillain-Barre syndrome (GBS) Chronic inflammatory demylinating polyneuropathy (CIDP) > Drug induced peripheral neuropathy Diabetic neuropathy Diabetic amyotrophy
The patient describes a chronic sensory deficit in a peripheral nerve distribution. This is most likely isoniazid-induced peripheral neuropathy, classically interfering with vitamin B6 via an unknown mechanism. As a result, pyridoxine should be regularly prescribed in all patients taking isoniazid. GBS and CIDP classically present as combined motor and sensory syndromes, of duration less than and more than 4 weeks respectively. While diabetes related peripheral neuropathy is possible, his glycosylated haemoglobin measurement, an accurate measure of the patients serum glucose levels over the past 3 months, reflects very good control.
Mononeuritis Multiplex - Example Question
A 53 year-old businessman presents to the neurology clinic complaining of weakness and numbness affecting his left hand. One month ago he was irritated when he noticed that the little finger of his left hand was often getting caught when he tried to put his hand in his pocket. Since then he has noticed progressive difficulty using the left hand, associated with an unpleasant tingling sensation.
In the last two weeks he has also noticed difficulty walking, and has tripped over on several occasions. When driving he finds that his right foot often becomes stuck behind the accelerator pedal and he struggles to lift it out.
On examination, in the left hand sensation to pin-prick is diminished over the little finger and medial side of the ring finger, as well as the medial side of the palm. There is weakness of finger abduction and adduction, but thumb abduction is normal. On examination of the legs, you note diminished sensation over the lateral aspect of the right calf, as well as the dorsum of the right foot. When asked to walk on his heels, he finds it difficult to do so, and trips over the right foot.
Investigations are as follows:
Haemoglobin 14.2 g/dl
WCC 7.1 x10^9/l
Platelets 420 x10^9/l
ESR 65 mm/hr
Na+ 139 mmol/l K+ 4.3 mmol/l Urea 13.2 mmol/l Creatinine 171 µmol/l Corrected calcium 2.26 mmol/l
ANCA Positive, with perinuclear staining pattern
PR3 antibodies Negative
MPO antibodies Positive
Urine dipstick +++ blood, +++ protein
Urine microscopy Red cell casts
Chest radiograph Clear
What is the most likely diagnosis?
> Microscopic polyangiitis Polyarteritis nodosa Wegeners granulomatosis Diabetes mellitus Entrapment neuropathy
This is mononeuritis multiplex with ulnar and common peroneal neuropathy. The causes of mononeuritis multiplex include vasculitis, diabetes, AIDS, amyloidosis, and rheumatoid arthritis.
The elevated urea and creatinine, haematuria with red cell casts, and proteinuria, all suggest glomerulonephritis. The combination of mononeuritis multiplex with glomerulonephritis strongly suggests systemic vasculitis. This is supported by the raised ESR.
Microscopic polyangiitis is a small-vessel vasculitis which is typically positive for p-ANCA, with antibodies against MPO (myeloperoxidase). Other features may include systemic symptoms such as fever, weight loss, and fatigue, as well as rash.
ANCA is negative in classic polyarteritis nodosa.
Wegeners granulomatosis often features upper airway disease, and is typically positive for c-ANCA, with antibodies against PR3.
Diabetes mellitus is a common cause of many peripheral neuropathies including mononeuritis multiplex, however there is nothing in the history to suggest this. Haematuria and red cell casts are not a typical feature of diabetic nephropathy, and neither is ANCA positivity.
Entrapment is a common cause of both ulnar and common peroneal neuropathy, but for both to occur simultaneously would be unusual.
