Presentation of hemiplegic migraine--hemiplegia and hemi-sensory loss following general anaesthesia.
We report a case of a 15-year-old male who developed severe left-sided hemiplegia and hemi-sensory loss 20 minutes after arrival in post anaesthetic care unit following an uneventful general anaesthesia for removal of a cannulated screw of left hip. Initial CT and MRI/MRA with diffusion-weighted imaging were unremarkable. The patient was transferred to The Royal Children's Hospital Melbourne and was commenced on heparin infusion pending investigation results. Complete recovery occurred within 36 hours. Eventually, hemiplegic migraine was diagnosed on the basis of negative investigations and a retrospective history of the patient's migraine. This case demonstrates that the management of peri-operative neurological deficits must be approached in a systematic fashion. Hemiplegic migraine is a well-defined clinical syndrome. It is not merely a diagnosis of exclusion.
Key Words: hemiplegic migraine, general anaesthesia, magnetic resonance imaging, magnetic resonance angiography, diffusion-weighted imaging
In the setting of general anaesthesia, both central and peripheral neurological deficits are rare presentations and a diagnostic challenge to anaesthetists from time to time (1). Rates of cerebrovascular events after general anaesthesia in patients with no known cerebrovascular diseases in non-neurological surgery and non-cardiovascular surgery range from 0.08 to 0.4% (2). Death or morbidity due to neurological events may ensue from inappropriate intervention or omission of active intervention by the anaesthetists (3). There is a wide range of causes which must be considered. Differential diagnoses should be approached in a systematic fashion. We describe a case of hemiplegic migraine that presented as severe left-sided hemiplegia and hemi-sensory loss in the immediate postoperative period.
A 15-year-old male weighing 69 kg presented for an elective removal of left hip cannulated screw for femoral epiphyseal slip. General anaesthesia was performed for the initial insertion of the screw in 2004, with no reported problems. Past history included mild asthma on seratide and salbutamol inhalers. He was not on any other medications and had no known drug allergies. No relevant history of migraine was disclosed at preoperative assessment. No premedication was given. General anaesthesia was induced with midazolam 2.5 mg, fentanyl 100 [micro]g, and propofol 150 mg given to allow insertion of an LMA size 4. Parecoxib 40 mg and paracetamol 1 g (IV) were given for analgesia.
Anaesthesia was maintained using oxygen, nitrous oxide and sevoflurane with spontaneous ventilation through a circle breathing system, and routine monitoring. Surgery was uneventful and lasted about 40 minutes. Anaesthesia was uneventful throughout with stable heart rate and blood pressure. End-tidal C[O.sub.2] ranged from 41 to 52 mmHg. He regained full consciousness about 20 minutes after arrival in the post-anaesthesia recovery ward and required morphine 20 mg in divided doses for analgesia.
He reported that his left arm and leg felt "weak" and "like sitting on air cushion". On examination, he had gross power deficit in his left arm (315) and left leg (1/5) and sensory loss in the left arm and leg with decreased pinprick, especially to light touch. Deep tendon reflexes were brisk and muscle tone was normal. His cranial nerves were intact. Initial assessments of his airway, breathing and circulation were satisfactory. The provisional diagnosis was left-sided hemiparesis and hemi-sensory loss due to a right cerebral vascular event. An immediate medical referral was made. A CT scan of the brain was normal. An MRI scan with diffusion-weighted imaging and magnetic resonance angiography (MRA) were performed which were normal. He was transferred to the Royal Children's Hospital (RCH) Melbourne on the evening of the same day.
On examination on arrival at 2000 h, he still had left-sided arm and leg weakness, but this had improved. An echocardiogram and bubble study were performed, which were normal with no evidence of thrombosis or shunting. Repeat MRI brain and MRA of the neck vessels showed no evidence of infarction and the carotid and cerebral vessels were normal. His admission comprehensive thrombophilia screen was also normal. A heparin infusion was commenced pending investigation results. His motor function recovered and he was back to his normal state within 36 hours of presentation. He was discharged home on aspirin which was to be continued for at least 12 months.
He represented to the RCH emergency three days later with episodes of dizziness associated with blurred vision lasting one to two seconds that were self-resolving. There was no associated numbness or weakness of his limbs. On examination, there were no other focal neurological signs. On further questioning, he gave a history of suffering from migraine since the age of 11 years, which he described as a throbbing headache, and being very noise sensitive. He usually had to lie in a quiet, dark room and the headaches resolved by the time he woke up. Based on the negative investigations, his self-resolving neurological status and the history of migraine headaches, hemiplegic migraine was diagnosed.
Hemiplegic migraine is a rare subtype of migraine and classified into two forms; familial and sporadic. Familial hemiplegic migraine (FHM) has an autosomal dominant trait. Sporadic hemiplegic migraine (SHM) with similar clinical symptoms but without other affected family members has been reported. FHM is genetically heterogeneous; there are three loci. The first gene identified was CACNA1A on chromosome 19p13 that encodes the [[alpha].sub.1A] -subunit of the P/Q-type voltage-gated calcium channel (VGCC). More recently, mutations in ATP1A2 on chromosome 1g23 that encode the [[alpha].sub.2]-subunit of the [Na.sup.+]/[K.sup.+] pump has been identified in a few families. Mutations in three different genes encoding structural proteins of P/Q (purkinje cell) type voltage-gated calcium channel and the membrane sodium-potassium ATPase pump have been implicated in FHM pathogenesis. SHM may reflect spontaneous mutations or incomplete penetration (4,5,18). P/Q-type VGCCs, which are distributed widely throughout the brain and are present at motor nerve terminals in the neuromuscular junction, play an integral role in presynaptic neurotransmitter release at nerve terminals (6). P/Q-type VGCCs regulate glutamine and other neurotransmitter release and play an important role in the regulation of excitability of cortical neurones, suggesting a possible mechanism for mediating cortical spreading depression, which is a depolarisation wave that propagates across the brain cortex at 2 to 3 mm/min and is associated with transient depression of spontaneous and evoked neuronal activity. During cortical spreading depression there is dramatic failure of brain ion homeostasis and efflux of excitatory amino acids from nerve cells (5,7,8). The presence of a P/Q-type VGCC abnormality may be involved in the early evolution of the migraine attack and possibly in the onset of cortical spreading depression, whereas a major site of action of ketamine is on the phencyclidine binding site of ligand-gated calcium channels. The propagation of cortical spreading depression is mediated via release of glutamine and aspartate from depolarised neurons and activation of neighboring neurons via N-methyl-D-aspartate (NMDA) receptors. Therefore, ketamine can exert an inhibitory effect on the propagation of cortical spreading depression wave via blockade of NMDA receptors (9). There is evidence that microinjection of opioid peptides into the neocortex and the hippocampus of experimental animals can elicit cortical spreading depression (10). Ketamine in analgesic dosage (25 mg) intranasally attenuated the spread of migraine in FHM, but not consistently in a small group study (9).
Only three cases similar to ours have been reported previously. Gil-Gouveia et al in 2004 reported a patient with a history of sporadic hemiplegic migraine following oesophagogastroscopy under sedation with midazolam and fentanyl who developed prolonged hemiparesis and hemisensory loss with horizontal nystagmus and reduced swallowing, whose motor function recovered after 43 days and headache resolved after 49 days (4). Thurlow in 1998 reported a patient with familial hemiplegic migraine following diagnostic laparoscopy under general anaesthesia with muscle relaxant who developed gross power deficit in four limbs (left> right) and left hemiparesis next day without headache, and whose motor function recovered within 48 hours (11). Strauss et al in 1989 reported a patient with recurrent headache following extraction of partially impacted wisdom teeth under sedation with midazolam and fentanyl who developed left hemiparesis with severe headache, and whose motor function recovered on the fifth day and headache persisted about six weeks (12). All cases were investigated with CT and MRI which were normal. One case was investigated with additional lumbar puncture, which was normal (12).
The provisional diagnosis in our patient was a right cerebral event due to intracerebral haemorrhage or ischaemic stroke. Clues from history and neurological examination are crucial. Prompt investigations are needed to exclude the diagnosis and differentiate critical diagnoses such as intracerebral haemorrhage, subarachnoid haemorrhage and ischaemic stroke, so that clinical intervention can be instituted accordingly. The differential diagnosis of intracerebral haemorrhage includes giant aneurysm, arteriovenous malformation, primary tumour and chronic subdural haematoma. Subarachnoid haemorrhage usually results from rupture of an intracranial aneurysm (75 to 80%) or arteriovenous malformation (5%). Mortality depends upon grading (grade 0-5). Subarachnoid haemorrhage was highly unlikely in our patient with no history of headache and negative CT, MRI and MRA. Lumbar puncture is only necessary in questionable circumstances (13).
The differential diagnosis of ischaemic stroke includes cerebral anoxia, cerebral thromboembolism, paradoxical embolism, occlusion or even dissection of neck arteries, haematological disorders, infective endocarditis and fat embolism after long bone surgery. Cerebral anoxia due to hypotension, hypoxaemia and cardiac dysrhythmias was excluded on the basis of intraoperative monitoring. Cerebral thromboembolism due to acute myocardial infarction or degenerative arterial disease was unlikely in this young patient without risk factors. CT/MRI with diffusion-weighted imaging excluded a cerebral infarct in our patient. Diffusion-weighted imaging can show abnormalities within minutes of stroke in animals, and presumably also in humans. Diffusion-weighted imaging assists in identifying small infarcts, which may be helpful in determining subsequent patient management and search for risks factors (1). Paradoxical embolism is another possibility in this setting. Twenty-five to 30% of patients have a probe-patent foramen ovale. If the right atrial is greater than the left atrial pressure (e.g. during a Valsalva manoeuvre), an embolus from deep venous thrombosis (thrombophilias, etc) or a fat embolus from a long bone could have entered the systemic circulation in our case. Although a patent foramen ovale is common in healthy individuals, it is most unusual for cerebral ischaemia to be caused by paradoxical embolism from the right to the left side of the heart. The risk of recurrent stroke in patients with a patent foramen ovale is probably low and far more information is required from randomised trials before embarking on routine surgical closure (1). An echocardiogram with bubble study was normal with no evidence of thrombosis or shunting in our patient. Carotid or vertebral artery dissection may be caused by faulty handling and positioning during general anaesthesia. Dissection of the wall of an internal carotid artery may cause a fairly distinctive headache syndrome, which is ipsilateral, involving the forehead periorbital region, face, teeth or neck, and has a burning or throbbing quality. The headache may be associated with an ipsilateral Horner's syndrome or monocular blindness, and contralateral focal neurological symptoms or signs. Dissection of the wall of a vertebral artery causes pain in the upper posterior neck and occiput, usually on one side, and may be associated with symptoms and signs of posterior circulation ischaemia, such as the lateral medullary syndrome. Vertebral artery dissection can also cause subdural haematoma (1).
In our patient, neck manipulation was minimal for inserting the LMA and the short duration of surgery was short. Furthermore, the MRA of neck vessels was normal. A haematological disorder may also exacerbate any ischaemia caused by co-existent thromboembolism or any other cause of cerebral ischaemia. More importantly, the haematological disorder needs treating in its own right (1).
The most important specific haematological factors for thromboembolism are thrombophilias. Acquired thrombophilia mainly comprises the antiphospholipid syndromes, characterised by the presence of lupus anticoagulant and anticardiopiin antibodies. Inherited protein C and S deficiency, antithrombin III deficiency, Factor 5 Leiden mutation and homocysteinaemia are possible causes" but were not present in our patient. Other common haematological disorders can be identified by routine first-line investigations. Infective endocarditis is a possible cause of perioperative stroke after general anesthesia. At any age, it is vital to diagnose infective endocarditis, as without treatment it can be fatal (1,15). There were no symptoms or signs to support infective endocarditis and the echocardiogram excluded this in our patient. Fat embolism was a remote possibility in our case which involved removal of a cannulated screw in the left hip. Fat embolism causes a devastating clinical deterioration within hours, characterised by signs including respiratory insufficiency (hypoxaemia [P.sub.a] [O.sub.2]< 60 mmHg; Fi[O.sub.2] [greater than or equal to] 0.4), central nervous system depression disproportionate to hypoxaemia, pulmonary oedema and axillary or subconjunctival petechiae, which were not present in our patient. MRI is the most sensitive imaging technique for diagnosing cerebral fat embolism".
Other possible causes that may present perioperative stroke-like syndromes include epilepsy (postictal weakness or Todd phenomenon), hemiplegic migraine, multiple sclerosis, peripheral nerve injury, metabolic abnormalities (hypoglycaemia, hypercalcaemia and hyponatremia), psychological (e.g. conversion disorder) or labyrinthine disorder (e.g. Meniere's disease, benign positional vertigo) (13,15). These were excluded on the basis of the history, clinical picture and our investigations.
Hemiplegic migraine is a subtype of migraine that may mimic cerebrovascular accident or transient ischaemic attack. Although rare, this phenomenon is well known to neurologists. There are several factors that may aid in the diagnosis of migrainous hemiplegia. Hemiplegic migraine occurs more predominantly in younger patients than does stroke. SHM has an age at onset before age 45 years (97%), whereas patients with SHM seldom have attacks beyond age 50 (17). There is rarely any history of other disease known to cause stroke. A family history of FHM and uncomplicated migraine may increase the index of suspicion for migraine. Additionally, most auras develop in a marching fashion in which the symptoms spread gradually. The march of symptoms is the most useful distinction between the focal neurological deficits caused by migraine and those caused by stroke (sudden onset) or seizures (spread over seconds). The headache usually follows the aura within 20 to 60 minutes and lasts between four and 72 hours. Some patients, however, do not have headache (12). Finally, investigations are required to exclude anything which can be associated or confused with migraine. Our patient was intensively investigated due to his age and the higher likelihood of an unusual (and often treatable) cause in young patients than in the elderly.
Our patient was commenced on a heparin infusion pending the results investigation. Heparin is used to reduce or reverse thrombotic occlusion of cerebral arteries and to prevent venous thromboembolism. However, heparin has several serious adverse side-effects, including acute bleeding. The benefits and risks in terms of heparin treatment should be balanced in individual patients according to data available (1,14). Clearly, the administration of heparin should be avoided if deemed unnecessary.
In summary, we report an unusual presentation of hemiplegic migraine, which was possibly precipitated by general anaesthesia, surgical stress or peroperative drugs. This case demonstrates that the management of peri-operative neurological deficits must be approached in a systematic fashion. We emphasise that appropriate intervention initiated by anaesthetists is vital, because the consequences of an incorrect diagnosis and its subsequent treatment can be devastating. Hemiplegic migraine is extremely rare. Nevertheless, consideration of this diagnosis is important, especially in a patient with a history of hemiplegic migraine or a strong family history of migraine.
We would like to thank Dr Tony Chow, staff anaesthetist at Box Hill Hospital and Dr Lloyd Shield, Neurologist at The Royal Children's Hospital for helpful advice, and to the patient's family for granting permission to report this case.
Accepted for publication on January 24, 2007.
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L. LIN *, C. ADEY ([dagger])
Department of Anaesthesia, Box Hill Hospital, Melbourne, Victoria, Australia
* M.D., B.App.Sc., Anaesthetic Registrar.
([dagger]) F.A.N.Z.C.A., Visiting Anaesthetist.
Address for reprints: Dr L. Lin, Department of Anaesthesia, Box Hill Hospital, Melbourne, Vic. 3128. email@example.com