Intravenous nimodipine worsening prolonged attack of familial hemiplegic migraine
© Springer-Verlag 2008
Received: 19 June 2008
Accepted: 11 September 2008
Published: 10 October 2008
We present a Norwegian family with familial hemiplegic migraine (FHM) with possibly four affected in three generations. The family had a point mutation in the ATP1A2 gene that caused a change of the amino acid valine to methionine (V628 M). The symptoms were pure FHM with intra- and interindividual variability, and epilepsy is not part of the clinical picture. Attacks could be provoked by physical activity. The proband had prolonged attacks of FHM, and was hospitalized due to such an attack provoked by a minor head trauma. The initial management was conservative, but due to persistence of the hemiplegia on day 9, a continuous nimodipine infusion was initiated in order to prevent cerebrovascular vasospasm. However, the nimodipine infusion worsened the patient’s symptoms and possibly provoked a generalized tonic–clonic seizure due to vasodilatation and reduced cerebral blood flow. The MRI showed cortical edema and the SPECT showed reduced perfusion on the contralateral side of the hemiplegia. We conclude that nimodipine is contraindicated in the management of prolonged FHM attacks, and recommend conservative management and supplement of sufficient intravenous fluid in nauseated patients in order to avoid hypovolemia.
KeywordsATP1A2 V628 M Cortical edema Hemiplegic migraine Migrainous infarction Nimodipine
Familial hemiplegic migraine (FHM) is an autosomal dominant rare type of migraine with aura characterized by some degree of hemiparesis . FHM1, FHM2 and FHM3 are caused by mutations in the ion-channel genes CACNA1A, ATP1A2 and SCN1A, respectively [2–4]. Some FHM families have mutations in yet unidentified genes. The majority of FHM families have pure FHM, but cerebellar ataxia is frequent in FHM families with mutation in the CACNA1A gene [5, 6].
A 16-year-old male was referred to the neurological ward on a hot summer day due to a prolonged attack of FHM. The patient had played soccer and shortly after heading a ball he experienced a left-sided homonymous hemianopsia, followed by left-sided sensory symptoms and motor weakness, and then a contralateral migrainous headache.
From the age of 2 years he experienced several attacks of sudden drowsiness, nausea and headache. Most attacks were preceded by head trauma and were interpreted as commotio. At the age of 6 years he also experienced motor weakness and reduced coordination of the hand during attacks, and at the age of 9 years this was followed by dysphasia and somnolence. Several CT-scans of the brain were normal. At the age of 10 years he had the diagnosis FHM after a prolonged attack with visual disturbances, scotoma, sensory symptoms, motor weakness, aphasia, somnolence and contralateral headache. The aphasia persisted for 3 weeks. The CT scan and the MRI were normal. He was discharged with 75 mg acetylsalicyl acid daily, and 160 mg propranolol daily. After initiation of the prophylactic treatment, the attack frequency 1–2 times per year was unchanged, but the duration of the aura symptoms and headache was reduced to 12 and 24–36 h duration, respectively.
Grandmother. The proband’s deceased grandmother on the mother’s side was reported to have had attacks of hemiplegia, but never had epileptic seizures.
Mother. The proband’s mother is 49 years old. She experienced her first attack at the age of 10 years. It usually started with unilateral sensory symptoms followed by unilateral hemiparesis and then she got a contralateral headache. Initially the attacks lasted up to 4 days and occurred from two to four times every month. The attack duration and frequency declined during adolescence, and she experienced her last attack at age 38 years. The attacks were often provoked by physical activity and the affected side varied between attacks. She had never had epileptic seizures.
Brother. The proband’s elder brother is 18 years old. He experienced his first attack at the age of 13 year and had not more than 15 attacks since then. The attacks usually start with dizziness followed by homonymous visual disturbances, unilateral sensory symptoms, aphasia and unilateral weakness and then a contralateral headache. The aura symptoms usually last from 1 to 6 h, while the headache last up to 24 h. The aura symptoms change side from attack to attack. The attacks are often provoked by physical activity. He never had any epileptic seizures.
Genetic testing showed a point mutation in exon 14 of the ATP1A2 gene. The nucleotide 1987 G > A substitution causes a change of the amino acid valine to methionine (V628 M). Both 16-year-old patients and mother had the mutation, while the elder brother was not tested.
We report a Norwegian family with FHM2 in possibly three generations. The phenotype–genotype correlation of the identified mutation (V628 M) is strengthened by the fact that it has also been reported in a Turkish family . The Norwegian family had attacks of pure FHM, with pronounced intra-familial variation in frequency, severity and duration of attacks. Physical activity provoked attacks in the affected alive, and mild head trauma provoked attacks in the proband. The symptomatology and variation are similar to that described in the Turkish family . Epileptic seizures were not reported in Norwegian nor the Turkish family. Mutations in the ATP1A2 gene usually cause pure FHM, but alternating hemiplegia of childhood, benign familial infantile convulsions, cerebellar symptoms, severe episodic neurological deficits and mental retardation have also been reported [8–18].
The hypovolemia caused by dehydration and arterial hypotension probably added to sustain the prolonged FHM attack, but these factors alone has not previously been sufficient to cause a generalized tonic–clonic seizure in the proband. The seizure is most likely caused by nimodipine, as the proband and his mother both noticed worsening of the aura symptoms after initiation of the intravenous nimodipine infusion. Nimodipine is a calcium-channel blocker that dilates cerebral vessels and it is used to prevent delayed cerebral ischemia following subarachnoid hemorrhage . In theory nimodipine might prevent the vasospasm of FHM by lowering Ca2+-influx. However, the continuous intravenous infusion of nimodipine probably aggravated the arterial hypotension, a known side effect. This caused additional hypoperfusion and hypoxia in the right hemisphere, which lead to a generalized tonic–clonic seizure and a secondary edema as shown on MRI and SPECT (for details see above). We conclude that nimodipine is contraindicated in the management of prolonged FHM attack, and recommend conservative management except from supplement of sufficient intravenous fluid in nauseated patients in order to avoid hypovolemia.
Conflict of interest
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