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 [ 24 ] .
the majority of fhm families have pure fhm , but cerebellar ataxia is frequent in fhm families with mutation in the cacna1a gene [ 5 , 6 ] .
we present a norwegian family with a v628  m mutation in the atp1a2 gene ( fig .  1 ) .
1the pedigree , the arrow indicate the proband , squares are men and circles are women , filled symbols are affected , and forward slash indicate deceased the pedigree , the arrow indicate the proband , squares are men and circles are women , filled symbols are affected , and forward slash indicate deceased
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 .
he was discharged with 75  mg acetylsalicyl acid daily , and 160  mg propranolol daily .
after initiation of the prophylactic treatment , the attack frequency 12 times per year was unchanged , but the duration of the aura symptoms and headache was reduced to 12 and 2436  h duration , respectively . prior to hospital admission
the patient barely drank or ate anything for 5  days due to nausea and severe migrainous headache . at first
, he received treatment with metoclopramide , paracetamole and ketobemidon and 1,000  ml i.v .
blood test including blood count , b-12 , creatine kinase , electrolytes , liver status , tsh , antinuclear antibodies , anticardiolipin antibodies and rheumatoid factor were all normal .
due to fear of vasoconstriction and migraine infarction , several measures were evaluated including continuous conservative management and verapamil treatment .
after external advice continuous infusion of intravenous nimodipine 510  ml / h ( dose ) was initiated .
the patient s symptoms worsened within hours , and the following morning he had a generalized tonic 
total infusion dose was then 16  mg . an acute mri showed mild swelling of the right parietal lobe ( figs .  2 , 3 ) .
he continued to have some degree of hemiparesis along with apraxia , homonymous hemianopsia and mild cognitive failure , i.e. , 25 of 30 points on the mini mental state examination ( mmse ) , and mildly impaired memory score and moderately impaired construction score on the cognistat . at that time
a single photon emission computed tomography ( spect ) showed reduced perfusion in the right hemisphere , predominantly in the temporal and parietal lobe ( fig .  4 ) .
the patient was discharged after 3  weeks hospitalization and re - admitted 4  weeks later on day 55 . at that time he suffered from dizziness and memory deficits .
clinical examination disclosed a partial homonymous hemianopsia , and the mmse score was 29 due to one point lost on the memory task .
this provoked an attack of 1-week duration , and he was advised to refrain from intensive physical activity.fig . 
2t2-weighted mri on day  10 showing hyperintensity and swelling of grey matter in the right temporal and parietal regionsfig . 
3apparent diffusion coefficient ( adc ) map on day 10 showing restricted diffusion in the right temporal and parietal regionsfig . 
499  m tc - hmpao - spect on day  22 showing cerebral blood flow hypoperfusion in the right hemisphere , predominantly in the temporal and parietal regions t2-weighted mri on day  10 showing hyperintensity and swelling of grey matter in the right temporal and parietal regions apparent diffusion coefficient ( adc ) map on day 10 showing restricted diffusion in the right temporal and parietal regions 99  m tc - hmpao - spect on day  22 showing cerebral blood flow hypoperfusion in the right hemisphere , predominantly in the temporal and parietal regions grandmother .
the proband s deceased grandmother on the mother s side was reported to have had attacks of hemiplegia , but never had epileptic seizures .
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 .
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 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 .
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 .
he was discharged with 75  mg acetylsalicyl acid daily , and 160  mg propranolol daily .
after initiation of the prophylactic treatment , the attack frequency 12 times per year was unchanged , but the duration of the aura symptoms and headache was reduced to 12 and 2436  h duration , respectively . prior to hospital admission
the patient barely drank or ate anything for 5  days due to nausea and severe migrainous headache . at first
, he received treatment with metoclopramide , paracetamole and ketobemidon and 1,000  ml i.v .
blood test including blood count , b-12 , creatine kinase , electrolytes , liver status , tsh , antinuclear antibodies , anticardiolipin antibodies and rheumatoid factor were all normal .
due to fear of vasoconstriction and migraine infarction , several measures were evaluated including continuous conservative management and verapamil treatment .
after external advice continuous infusion of intravenous nimodipine 510  ml / h ( dose ) was initiated .
the patient s symptoms worsened within hours , and the following morning he had a generalized tonic 
total infusion dose was then 16  mg . an acute mri showed mild swelling of the right parietal lobe ( figs .  2 , 3 ) .
he continued to have some degree of hemiparesis along with apraxia , homonymous hemianopsia and mild cognitive failure , i.e. , 25 of 30 points on the mini mental state examination ( mmse ) , and mildly impaired memory score and moderately impaired construction score on the cognistat . at that time
a single photon emission computed tomography ( spect ) showed reduced perfusion in the right hemisphere , predominantly in the temporal and parietal lobe ( fig .  4 ) .
the patient was discharged after 3  weeks hospitalization and re - admitted 4  weeks later on day 55 . at that time he suffered from dizziness and memory deficits .
clinical examination disclosed a partial homonymous hemianopsia , and the mmse score was 29 due to one point lost on the memory task .
this provoked an attack of 1-week duration , and he was advised to refrain from intensive physical activity.fig . 
2t2-weighted mri on day  10 showing hyperintensity and swelling of grey matter in the right temporal and parietal regionsfig . 
3apparent diffusion coefficient ( adc ) map on day 10 showing restricted diffusion in the right temporal and parietal regionsfig . 
499  m tc - hmpao - spect on day  22 showing cerebral blood flow hypoperfusion in the right hemisphere , predominantly in the temporal and parietal regions t2-weighted mri on day  10 showing hyperintensity and swelling of grey matter in the right temporal and parietal regions apparent diffusion coefficient ( adc ) map on day 10 showing restricted diffusion in the right temporal and parietal regions 99  m tc - hmpao - spect on day  22 showing cerebral blood flow hypoperfusion in the right hemisphere , predominantly in the temporal and parietal regions
the proband s deceased grandmother on the mother s side was reported to have had attacks of hemiplegia , but never had epileptic seizures . mother .
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 .
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 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 .
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 .
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 [ 818 ] .
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 
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 ca - 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 .
 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 . 
Introduction
Case reports
Proband
Family history
Genetic testing
Discussion