Guillain-Barre and Miller-Fisher Syndrome Flashcards
Guillain-Barre Syndrome - Pathogenesis
Guillain-Barre syndrome describes an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni)
Pathogenesis
cross reaction of antibodies with gangliosides in the peripheral nervous system
correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated
anti-GM1 antibodies in 25% of patients
Miller-Fisher Syndrome
Miller Fisher syndrome
variant of Guillain-Barre syndrome
associated with ophthalmoplegia, areflexia and ataxia. The eye muscles are typically affected first
usually presents as a descending paralysis rather than ascending as seen in other forms of Guillain-Barre syndrome
anti-GQ1b antibodies are present in 90% of cases
Miller-Fisher Syndrome: Example Question
A 45-year-old lady was admitted to the Medical Admission Unit with a 16-hour history of weakness. Two days prior to the admission she experienced a sensation of double vision and shortly afterwards had become more unsteady when walking. The weakness developed initially in her arms and was shortly followed by weakness in her legs. Her past medical history included a history of coeliac disease for which she adhered to a strict gluten-free diet, but she was otherwise fit and well.
On examination, she was not distressed and was fully orientated to her surroundings. She had a temperature of 37.6ºC, a heart rate of 88/min, a respiratory rate of 18/min and a blood pressure of 182/82 mmHg. The cardiovascular and respiratory examination was otherwise unremarkable. Examination of the abdomen revealed a mass arising from the symphysis pubis. Examination of her cranial nerves revealed a failure of bilateral external gaze, as well as diplopia on asking the patient to fixate down and in. Her pupils were dilated but reactive. Fundoscopy revealed no abnormalities, and cranial nerve examination was otherwise unremarkable. The tone was reduced in all muscle groups, with a power of grade 3/5 in all muscle groups. Reflexes were absent in all limbs and plantar responses were normal. She was unable to mobilise independently and an ataxia was noted.
Initial investigations revealed the following:
Hb 132 g/l
Platelets 222 * 109/l
WBC 5.8 * 109/l
ESR 16 mm/hr
Na+ 139 mmol/l K+ 3.7 mmol/l Urea 4.3 mmol/l Creatinine 77 µmol/l Bilirubin 11 µmol/l ALP 101 u/l ALT 22 u/l Glucose 6.0 mmol/l CRP 22 mg/l
Appearance Clear
Glucose 4.5 mmol/l
Protein 0.6 g/l
White cells 3 / mm³
CT brain scan: normal appearances, no evidence of haemorrhage, midline shift or space occupying lesion.
What is the single investigation most likely to lead to a diagnosis?
Anti Jo1 antibodies Anticholinesterase antibodies > Anti GQ1b antibodies Anti GM1 antibodies Antinuclear antibodies
The combination of ophthalmoplegia, ataxia and areflexia is strongly suggestive of Miller-Fisher syndrome, a variant of Guillain-Barre syndrome (GBS). Anti GQ1b antibodies are present in 90% of cases. Anti GM1 antibodies are present in axonal neuropathies including GBS but also other conditions and are not specific to Miller Fisher syndrome. Anti Jo1 antibodies are found in polymyositis whilst anticholinesterase antibodies are found in myasthenia gravis.
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
Prognosis: 20% suffer permanent disability, 5% die
Miller-Fisher Syndrome: Example Question
A 42 year old male presents with double vision and weakness in his fingers, which he noticed when he repeated dropped his pen when trying to write at work. His symptoms appear to have onset over the past few days. He has no past medical history other than a recent episode of diarrhoea and vomiting about two weeks ago. He reports no limb weakness and no sensory loss. He denies any back pain or palpitations. On examination, there is a 3/5 weakness in finger flexion, finger extension and wrist extension in both hands, with no fatiguability. No reflexes present in the lower or upper limbs. There is no ptosis or nystagmus but reduced eye movements in all directions. His finger-nose test demonstrates reduced coordination bilaterally and the patient has too little confidence to walk. Which investigation is diagnostic?
Anti-GM1 antibody > Anti-GQ1b antibody MRI brain and whole spine Anti-MUsK (muscle specific kinase) antibody Anti-acetylcholine receptor antibody
The patient has presented with a classic triad of ophthalmoplegia, ataxia and areflexia, which should suggest Miller-Fisher syndrome, an acute onset demyelinating peripheral neuropathy recognised as a variant of Guillain Barre Syndrome. Anti-GQ1b antibody is present in between 85-90% of patients with Miller-Fisher syndrome1.
Key differentials of MFS include myasthenia gravis, brainstem infarcts and brainstem encephalitis. In this case, the absence of fatiguablity and nystagmus rule against neuromuscular junction disorders and brainstem events respectively.
Miller-Fisher Syndrome: Classic Triad
OPTHALMOPLEGIA
ATAXIA
AREFLEXIA
Key Differentials of Miller-Fisher Syndrome
Myasthenia Gravis
Brainstem Infarcts
Brainstem Encephalitis
Guillain-Barre Syndrome - Example Question
A 35-year-old female presents to the Emergency Department with worsening lower limb weakness over a three day period. She is now unable to walk and feels that her fingers are becoming clumsy. On examination her heart rate is 65 beats per minute and regular, her blood pressure is 125/70 mmHg and her respiratory rate is 20 breaths per minute. She has absent ankle and knee jerks and reduced reflexes in the upper limbs.
Her cerebrospinal fluid (CSF) study shows an elevated protein with a normal white cell count. Given her likely diagnosis, which of the following parameters is most important to measure throughout her admission?
Lower limb power Serial CSF protein levels Forced expiratory volume over 1st second (FEV1) Postural blood pressure > Forced vital capacity (FVC)
The most common cause of death in patients with the severe Guillain-Barre Syndrome (GBS) is respiratory failure. This is due primarily to weakness in chest wall muscles, but may also be due to bulbar dysfunction and aspiration. Patients may require intensive care admission and ventilatory support.
For this reason, it is of great importance that forced vital capacity (FVC) is measured on a routine basis and results documented so that additional support can be sought as soon as possible. FEV1 may be preserved in early deterioration as it is not a measure of vital capacity or a marker of chest wall expansion. Therefore, a reduction in FVC is a more sensitive marker of deterioration.
Most Common Cause of Death in Guillain Barre ?
The most common cause of death in patients with the severe Guillain-Barre Syndrome (GBS) is respiratory failure. This is due primarily to weakness in chest wall muscles, but may also be due to bulbar dysfunction and aspiration. Patients may require intensive care admission and ventilatory support.
For this reason, it is of great importance that forced vital capacity (FVC) is measured on a routine basis and results documented so that additional support can be sought as soon as possible. FEV1 may be preserved in early deterioration as it is not a measure of vital capacity or a marker of chest wall expansion. Therefore, a reduction in FVC is a more sensitive marker of deterioration.
Guillain Barre Syndrome - Example Question IV Immunoglobulins vs Plasma Exchange
A 28-year-old male presents with feet, hand and perioral paresthesia associated with progressive weakness in his lower limbs over approximately two weeks. On examination he has normal tone and reduced reflexes in his lower limbs, reduced proprioception in feet and hands, and proximal weakness in his lower limbs. His MRI spine was unremarkable.
Other results:
CSF protein 2.0g/L
HIV negative
Lyme serology negative
Epstein-Barr virus negative
What is the correct treatment?
> Intravenous immunoglobulins Intravenous methylprednisolone Cyclophosphamide infusion Pyridostigmine Doxycycline
The history given is one typical of Guillain-Barré syndrome with the characteristic albuminocytological dissociation within the CSF (a raised protein with a normal white cell count). After assessing for respiratory dysfunction, arrhythmias and autonomic dysfunction the appropriate treatment is intravenous immunoglobulins. This has been shown to hasten recovery in patients who are either not spontaneously improving or unable to walk unaided if used within 4 weeks of neuropathic symptom onset, with better outcomes for earlier use. Plasma exchange is also another option in these patients but intravenous immunoglobulins tend to be used because they are as effective as plasma exchange. No benefit in combining both treatments. IVIG may be easier to administer and tends to have fewer side-effects
Intravenous methylprednisolone has not been shown to be beneficial, and would tend to be used in a multiple sclerosis flare. Equally, immunosuppression with cyclophosphamide is not typically used.
Use of doxycycline may be considered if Lyme disease is diagnosed, which manifest with a range of neurological signs and symptoms. Pyridostigmine would used in myasthenia gravis patients, and therefore would not be used in this case.
GB - Diagnosis
A 45-year-old male presents with ascending weakness. He first noticed that he was tripping over more easily, but now has trouble getting out of a chair. He feels otherwise well. Of note, he did have moderate diarrhoea which had completely resolved a week prior to developing this weakness.
On examination, he is haemodynamically stable with a heart rate of 68 beats per minute and a blood pressure of 135/80 mmHg. His respiratory rate is 18 breaths per minute. He has reduced power in ankle plantar and dorsiflexion bilaterally, absent ankle jerks and reduced knee jerks. His plantar responses are downwards.
Acutely, which of the following results will most assist you with a diagnosis?
MRI showing inflammation of the lumbo-sacral spinal cord Elevated white cell count on cerebrospinal fluid (CSF) analysis Abnormal nerve conduction tests of the lower limbs > Elevated CSF protein Raised erythrocyte sedimentation rate (ESR)
Acutely, an elevated CSF protein level may be the only indication of an inflammatory aetiology, highly suggestive of Guillain-Barré Syndrome (GBS) or Acute Inflammatory Demyelinating Polyradiculoneuropathy in this clinical setting. The CSF white cell count is not elevated in GBS.
In relation to nerve conduction studies, these often provide normal results within the acute setting and the classic demyelination findings may not be detectable for at least a week.
Miller Fischer Syndrome Diagnosis: Example Question
A 67 year-old woman presents to hospital after a collapse at home. One week earlier she had seen her own doctor after feeling generally unwell with fever, myalgia, and coryza. These symptoms were attributed to a viral infection and have now resolved. However, for the past few days she has felt unsteady on her feet and has had to hold on to the furniture whilst walking around the house. For the last two days in particular she has also noticed that her vision has deteriorated, and she has been seeing double. Today she tried to hold onto the sofa whilst walking around the room, but misjudged the distance and lost her grip, causing her to fall to the floor. Her daughter who is also present adds that she feels her mothers speech is slurred compared to normal, and has been so for the past three days.
Her past medical history includes hypertension, hypothyroidism, type 2 diabetes, hyperlipidaemia, angina, and recurrent urinary tract infection. She takes ramipril, amlodipine, doxazosin, laevoythyroxine, metformin, gliclazide, simvastatin, atenolol, nicorandil, and nitrofurantoin. She does not smoke but admits to enjoying a glass of sherry on most nights. Usually she is independently mobile, without aids. She lives on her own and is self-caring.
On examination, there are some bruises on the left shoulder where she fell, but no suggestion of any fracture. Observations are normal and she is afebrile. Cardiovascular, respiratory, and abdominal examination is unremarkable. She is fully alert and oriented. Pupils are equal and reactive to light. Eye movements are grossly impaired in all directions. There is no facial asymmetry. Muscle power is normal in all limbs, but finger-nose pointing is impaired and she is unable to walk in a straight line. Reflexes are unobtainable. Sensation is normal.
What is the most likely diagnosis?
Wernickes encephalopathy Viral cerebellitis Myasthenia gravis > Miller Fisher syndrome Posterior circulation stroke
There has been a subacute deterioration in global cerebellar function, as suggested by gait ataxia, bilateral upper limb dysmetria, and dysarthria, progressing over a period of days. There is also complete ophthalmoplegia, and absence of reflexes. This combination of features occurring after a recent viral infection suggests a diagnosis of the Miller Fisher variant of Guillain-Barré syndrome. One might also expect to find descending weakness, which was not present in this case. Confirmation of the diagnosis is by lumbar puncture which demonstrates raised protein with normal cell count, and positive serum anti-GQ1b antibodies. Treatment is as for Guillain-Barré syndrome, with supportive care and intravenous immunoglobulin or plasmapheresis.
Wernickes encephalopathy presents with ataxia and ophthalmoplegia but also confusion, and typically occurs in malnourished alcoholics.
Viral cerebellitis is more common in children and would not explain the ophthalmoplegia and areflexia.
Myasthenia gravis would be unlikely to develop so rapidly, and though a cause of complex ophthalmoplegia, it would not explain the areflexia or the cerebellar signs.
Posterior circulation syndromes can cause acute cerebellar dysfunction but stroke of any sort is unlikely as this is a subacute presentation of neurological features not referable to one part of the brain.
GB and Temporary Autonomic Neuropathy: Example Question
An urgent medical consult was requested regarding a 52-year-old female who had been admitted to the neurology ward a few hours previously and who had developed hypotension. She had presented to the Emergency Department with new weakness in her legs that had occurred over a course of three days. She also complained of continual lower back pain and pain in the top of her thighs, and as her illness progressed she was no longer able to weight bear. She had a past medical history of hypothyroidism, for which she was prescribed levothyroxine 125mcg OD, and other than an episode of viral gastroenteritis diagnosed by her GP two weeks prior to her current admission she was fit and well. Upon transfer to the neurology ward blood investigations, a chest x-ray, CT head scan and lumbar puncture were performed, the results of which are as follows:
Hb 132 g/l
Platelets 248 * 109/l
WBC 8.2 * 109/l
Na+ 138 mmol/l K+ 5.2 mmol/l Urea 6.4 mmol/l Creatinine 77 µmol/l CRP 15 mg/l Glucose 7.2 mmol/l TSH 0.26 (NR 04-3.6 mu/l) Free T4 10.6 (NR 10 - 20 pmol/L)
Autoantibody screen: awaiting results
Urinalysis: negative
Urine MCS: awaiting results
Blood MCS: awaiting results
Chest x-ray: normal appearances of heart and lung fields
CT head: normal intracranial appearances
Lumbar puncture:
Protein 0.8g (NR 0.2-0.4 g/L) Glucose 6.3 (blood glucose 7.2) WCC 8 (<5/mm³) Opening pressure 15 (NR 10-20 cmH2O) Microscopy nil seen, awaiting culture and sensitivity result
Whilst awaiting definitive measurement her blood pressure was noted to fluctuate between 55/30 mmHg and 162/84 mmHg within a matter of minutes; at present her blood pressure was 62/42 mmHg. Upon examination of her cardiovascular system, she was clinically well perfused with a normal and palpable radial pulse, a JVP of 3cm and a peripheral and central capillary refill time of less than two seconds. He heart rate was 82 bpm. Examination of her respiratory system was unremarkable with no respiratory distress, a respiratory rate of 16/min and oxygen saturations of 99% on air. Examination of her gastrointestinal system was unremarkable. Examination of her peripheral nervous system revealed a power deficit of grade 2/5 in all muscle groups of the lower limbs, power 5/5 in the upper limbs and normal sensation and coordination throughout. Knee and ankle reflexes were absent bilaterally. Cranial nerve examination was unremarkable.
What is single next best step with regards to management of her blood pressure?
Commence dobutamine infusion Commence noradrenaline infusion Commence intravenous fluid resuscitation with 500ml of colloid stat > Commence intravenous immunoglobulin Arrange urgent plasmapheresis
This lady has developed Guillain Barre Syndrome (GBS) with evidence of a temporary autonomic neuropathy, as manifested by her highly labile blood pressure. The treatment of this is therefore to treat the underlying disorder, which in this instance is with intravenous immunoglobulin. In the presence of GBS complicated by autonomic neuropathy blood pressure is not a reliable indicator and any thus any decisions regarding fluid status must be in concordance with clinical examination findings. In this question, she is clearly euvolaemic clinically and so there is no indication for fluid or inotropic support.
Guillain-Barre Sx
- Progressive weakness of all 4 limbs
- Classically ASCENDING pattern of weakness i.e. lower extremities affected first BUT proximal lower limb muscles affected earlier than distal
- Sensory Sx are mild e.g. distal paraesthesia
- Some patients experience back pain in initial stages
- Areflexia
- CN involvement eg Diplopia
- Autonomic involvement e.g. Urinary Retention
GB - Presentation
Hx of rapidly progressive bilateral leg weakness e.g. after a diarrhoea illness 3-4 weeks before
Examn: - Lower limb LMN signs > Hyporeflexia > Flaccid paralysis \+ Tachycardia \+ Urinary Retention
(NB Hyperreflexia is seen in GBS variant Bickerstaff’s Encephalitis)
