Paraneoplastic Neurological Syndromes Flashcards
Lambert-Eaton Syndrome
Lambert-Eaton myasthenic syndrome
seen in small cell lung cancer
antibody directed against voltage gated calcium channel
similar features to myasthenia gravis
proximal muscle weakness, hyporeflexia and autonomic features (dry mouth, impotence etc)
Other Paraneoplastic Neurological Syndromes
Other syndromes may be associated with detectable antibodies, for example:
anti-Hu: small cell lung cancer - painful sensory neuropathy, cerebellar syndromes, encephalitis
anti-Yo: ovarian, breast cancer - cerebellar syndrome
anti-Ri: small cell lung cancer - retinal degeneration
Paraneoplastic Neurological Syndrome - Example Question
A 57 year-old smoker presents to you with difficulty walking. He used to be able to mobilise unaided but recently he has required the assistance of his wife. He reports being more clumsy than usual. He drinks 3 cans of larger every month. He takes simvastatin for high cholesterol and has been taking aspirin for 10 years since his GP started it. He has lost a lot of weight in recent months, which he can’t quantify.
On examination you find that he is cachectic. He has an intention tremor and exhibits dysdiadochokinesia. His gait is broad based. He has bilateral nystagmus on horizontal gaze. On auscultating his chest you find he has a degree of bronchial breathing on the right middle lobe.His observations are unremarkable.
His blood tests are as follows:
Hb 100 g/l MCV 79.9 fL Platelets 239 * 109/l WBC 6.6 * 109/l Na+ 134 mmol/l K+ 4.3 mmol/l Urea 6 mmol/l Creatinine 88 µmol/l anti-Hu antibody POSITIVE Bilirubin 6 µmol/l ALP 62 u/l Albumin 29 g/l
CT head: No acute intracranial pathology.
What is the most appropriate investigation?
> Chest X-ray Vitamin B12 levels ECG Visual evoked potentials Muscle biopsy
This gentleman presents with signs and symptoms of the cerebellar syndrome.
He is cachectic, has a history of smoking and some signs of his chest which would raise concern given his history. Another important clue in the question is the presence of anti hu antibodies, which are associated with paraneoplastic cerebellar syndrome secondary to small cell lung cancer. Given the history and examination findings it is paramount to perform an X-Ray of his chest, and should that be inconclusive he will require a high resolution CT scan.
An intracranial lesion, such as a tumour or a vascular event is also unlikely, given the normal CT head result and bilateral presentation.
He is has a history of excessive alcohol intake, which can also cause the cerebellar syndrome.
Vitamin B12 deficiency is associated with subacute combined degeneration of the cord. This would present with upper and motor neuron deficits and a sensory neuropathy. It would not present with isolated cerebellar signs.
Anti-NMDA Receptor Encephalitis
Anti-NMDA receptor encephalitis is a paraneoplastic syndrome, presenting as prominent psychiatric features including agitation, hallucinations, delusions and disordered thinking; seizures, insomnia, dyskinesias and autonomic instability. Ovarian teratomas are detected in up to half of all female adult patients, particularly prevalent in Afro-Carribean patients1. MRI head can be normal but abnormalities can be visualised on FLAIR sequences in the deep subcortical limbic structures2. CSF may demonstrate pleiocytosis but can be normal initially. Anti-MuSK is an autoantibody specific to muscle kinase in myasthenia gravis with no evidence of a thymoma and without antibodies to acetylcholine receptors. Anti-GM1 is an autoantibody specific to acute inflammatory demyelinating polyneuropathy (AIDP) variant of Guillain-Barre syndrome.
Treatment of anti-NMDA encephalitis is based of immunosuppresion with intravenous steroids, immunoglobulins, rituximab, cyclophosphamide or plasma exchange, alone or in combination. Resection of teratoma is also therapeutic.
Lambert Eaton Syndrome
Seen in association with SCLC and to a lesser extent breast and ovarian Ca
May also occur independently as an auto-immune disorder - caused by antibody directed against pre-synaptic voltage gated Ca2+ channel in the peripheral nervous system
Features:
- Repetitive muscle contractions lead to increased muscle strength (NB In contrast to MG)
In reality this is only seen in 50% patients and following prolonged muscle use strengths will eventually decrease
- Limb girdle weakness (affects lower limbs first)
- Hyporeflexia
- Autonomic Sx: Dry mouth, Impotence,, Difficulty micturating
- Ophthalmoplegia and ptosis NOT commonly a feature (unlike in MG)
EMG: Incremental response to repetitive electrical stimulation
Mx:
- Treatment of underlying Ca
- Immunosuppression eg prednisolone or azathioprine
- IV immunoglobulins and plasma exchange
- 3,4- diaminopyridine currently being trialled > works by blocking K+ channel efflux in nerve terminal so that action potential duration is increased therefore Ca2+ channels can be open for longer and there is greater acetylcholine release to stimulate muscle
Muscle Weakness - Paraneoplastic Syndrome: Example Question
A 62-year-old gentleman is seen at the respiratory clinic after a mass lesion is identified by his GP on chest x-ray. He is a heavy smoker and has had a cough and weight loss for the past two months. On further questioning, he admits to feeling very weak and is having difficulty getting out of a chair. On examination, the consultant notices some proximal muscle wasting. Initial investigations reveal a blood pressure of 170/90mmHg and a low potassium. In addition to organising staging CT and bronchoscopy, he requests a 24-hour urinary cortisol test, which is raised.
Which of the following is the most likely underlying pathology?
Squamous cell bronchial carcinoma Large cell bronchial carcinoma Carcinoid tumour > Small cell bronchial carcinoma Bronchial adenocarcinoma
The 24-hour urinary cortisol result here suggests a diagnosis of Cushing’s syndrome. The co-existant presentation of lung cancer points to paraneoplastic Cushing’s syndrome. The vast majority of paraneoplastic syndromes seen in lung cancer are caused by small cell bronchial carcinoma, a neuroendocrine tumour which can secrete a variety of hormones or antibodies. In paraneoplastic Cushing’s syndrome, ectopic adrenocorticotrophic hormone (ACTH) production results in a syndrome characterised by muscle weakness, hypertension, hypokalaemia and oedema. The classical features of buffalo hump and moon face are often absent.
