vasospasm ( vsp ) is one of the major causes for prolonged neurologic deficit in patients with aneurysmal subarachnoid hemorrhage.1 treatment of vsp is therefore one of the main priorities for these patients .
balloon angioplasty or stenting are options for vsp of the proximal vessels , whereas distally located vsp is preferably treated pharmacologically.2 a long list of pharmacologic agents has been tested for their effect on vsp .
intravenous ( iv ) or oral application of nimodipine combined with triple h therapy ( hypertension , hypervolemia , hemodilution ) is currently recommended as the first - line prevention for vsp.3 in patients not responding to this preventive therapy , short local intra - arterial nimodipine administration ( slina ) is recommended , although it is often only effective during the time of infusion.4 however , intra - arterial ( ia ) nimodipine administration may be prolonged for a few days .
few case series have reported about the feasibility , efficacy , and safety of this treatment , and standardized guidelines are lacking.5 
 6 
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  we report our experience with continuous local intra - arterial nimodipine administration ( clina ) via a catheter in the internal carotid artery ( ica ) in refractory cerebral vsp .
a 40-year - old woman was referred to our hospital due to headache and nausea that started acutely the day of admission . she had no history of hypertension or other diseases but was a former smoker .
native computed tomography ( ct ) scan showed a subarachnoid hemorrhage ( sah ) extending to the suprasellar cisterns and both sylvian fissures ( modified fisher grade 4 ) .
the hunt & hess grade was 2 , and the glasgow coma scale and the world federation of neurosurgery grade were 15 and 1 , respectively .
ct angiography ( cta ) revealed a saccular aneurysm of the anterior communicating artery ( acom ) ( fig .
the aneurysm was located at the most distal acom segment , at the origin of the left anterior cerebral artery a2 segment ( fig .
1 ) . 
 ( a ) three - dimensional angiography of left carotid artery showing an anterior communicating artery aneurysm measuring 3    7 mm .
the aneurysm was successfully treated by coil embolization , and the patient was asymptomatic after the procedure . according to the department 's standard post - sah treatment protocol , the patient was given continuous iv nimodipine , fluids , and statins . at day 6
, the patient developed hemiparesis predominantly affecting the right arm and severe expressive aphasia corresponding to a national institute of health stroke scale ( nihss ) score of 6 ( facial palsy 1 ; arm 2 ; leg 1 , aphasia 2 ) .
cta showed vsp in the intracranial ica , the anterior cerebral artery proximal segment ( a1 ) , and the middle cerebral artery proximal segment ( m1 ) bilaterally , but predominantly on the left side .
vsp was present also in the basilar artery and the left posterior cerebral artery . at day 7 , 30-minute ia administration of 4  mg nimodipine in the left intracranial ica and 30 minute ia administration of 4  mg nimodipine in the left intracranial vertebral artery led to a clear improvement of angiographic vsp and neurologic impairment . due to the recurrence of symptoms at day 8
, 30-minute ia administration of 4  mg nimodipine in the left intracranial ica and in the left intracranial vertebral artery were repeated with beneficial but transitory effect . at day 9 ,
1 hour ia administration of 8  mg nimodipine followed by 3-minute ia administration of 30  mg papaverine were performed .
digital subtraction angiography ( dsa ) showed partial resolution of vsp in the left m1 and a1 but persistent vsp in the left m2 and a2 ( fig .
2 ) . 
 left carotid angiogram at the initiation of continuous local intra - arterial ( ia ) nimodipine infusion day 9 ( three short local ia nimodipine administrations were done on days 7 , 8 , and 9 after coil embolization ) .
( a ) severe vasospasm is seen in the a1 , a2 , and m2 branches .
( b ) partial resolution after 4  mg nimodipine in 30 minutes but still severe vasospasm in a2 .
transcranial color - coded sonography ( tccs ) measurements of blood flow velocity in the left distal m1 showed no changes before and after ia treatment ( fig .
3 ) . two hours later , cerebral mri showed multiple watershed infarcts in the left carotid artery territory and in the left parietal lobe ( fig .
4 ) . 
 mean velocity in the left distal m1 segment measured with transcranial color - coded sonography . 

diffusion - weighted magnetic resonance imaging day 9 showed scattered cortical infarctions in the left hemisphere .
the patient was quickly referred to tccs that showed marked worsening of hemodynamics ( mean velocity of 300 cm / s in the left distal m1 , lindegaard index  >  7 ) .
clina was established by introducing a microcatheter ( progreat 2.7f , terumo interventional system , tokyo , japan ) into the left ica through a guiding catheter . with the microcatheter in place
nimodipine dose was set at 2 mg / h . an iv bolus dose of 5000 ie heparin was administered initially , followed by 1500 to 2500 units / h to keep the activated clotting time > 200 s. a few hours later , the patient showed improvement of symptoms with normalized motor function and only a slight residual aphasia ( nihss  =  1 ) . at day 10
, clina was stopped , the catheter and the sheath were removed , and the full dosage ( 2 mg / h ) was given iv for 7 days and then orally for another 7 days .
in addition to nimodipine , advanced vsp treatment including pressor , fluids , statins , magnesium , and dantrolene was administered . during the hospital
stay a lumbar drain was inserted due to transient hydrocephalus , and antibiotics were given due to a urinary tract infection .
she had no measurable speech impairment but a slight disturbance of fine motor skills in the right hand , and she complained about gait instability and dysesthesia in the right hemibody ( nihss  =  0 ) . at follow - up day 90 , the patient reported reduced stamina , mild headache , and non  drug - demanding neuropathic pain in the right arm .
motor function was normalized , and she had no apparent speech impairment ( nihss  =  0 ) .
tccs showed normal blood flow velocities in all intracranial arteries , and mri showed no new ischemic lesions .
this is the first case of continuous local intra - arterial nimodipine administration ( clina ) for refractory vsp described in scandinavia .
the treatment had a dramatic effect on both angiographic vsp and neurologic impairment with no complications .
in line with earlier reports,5 
 6 
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 10 our case shows that clina is feasible , safe , and may be effective in patients with symptomatic medically refractory vsp following sah . however , there is no consensus when to start the treatment .
although other reports recommend starting clina if 30-minute ia nimodipine administration does not show improvement of vsp , the threshold for referring patients to dsa is not always specified . in some earlier reports
, patients were referred to dsa either after a decline in the parameters of multimodal neuromonitoring or after progressive loss of consciousness postoperatively.5 
 7 
 8 in another report , the patients underwent dsa within the first 2 hours after onset of clinical symptoms and decrease in brain tissue oxygen.6 in our patient , clina was started 2 days after the first focal neurologic impairment .
the two slinas performed at day 7 and day 8 showed good angiographic response and partial clinical improvement .
the third slina showed partial resolution of angiographic vsp with no clinical and doppler response , and mri showed established cerebral infarction . in an earlier study ,
21 of 25 patients treated with clina developed cerebral infarction secondary to vsp,7 and , similarly to our case , the mean onset of clina was 9.19    3.31 days . in another case
series of 6 patients , onset of clina was 7.5    2.06 days , and none of the patients had cerebral infarction.6 
  due to the possibly high safety profile and efficacy of the treatment , it may therefore be appropriate to refer patients promptly to dsa and clina in case of development of focal neurologic impairment6 to prevent ischemic complications .
transcranial ultrasound has a high specificity ( 99% ) and positive predictive value ( 97% ) for the detection of vsp in the middle cerebral artery11 and is of established value in the detection and monitoring of vsp after sah ( strong recommendation , class i 
ii evidence).12 
 13 in our case , there was a good correlation between ultrasonographic findings , clinical impairment , and dsa .
future studies should investigate if tccs may play a major role in the early selection of patients who will benefit from this treatment .
there are no standardized guidelines for patient selection , the start and the duration of clina , as well as for the dosage of nimodipine and heparin .
clina is an expensive and resource - demanding procedure requiring specialized intensive care with a multidisciplinary team of anesthesiologists , neuroradiologists , neurosurgeons , and the availability of multimodal neurologic monitoring .
wall dissection , catheter dislocation , sepsis , air emboli , and embolic infarction due to thrombotic adhesion at catheter or vessel wall are all potential complications of clina .
moreover , a too high nimodipine dose may lead to hypotension , whereas inappropriate heparin dosage may lead to either thromboembolic or hemorrhagic complications .
none of the earlier studies has reported complications.5 
 6 
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 8 however , there are no conclusive data about the safety of clina because all the current evidence is based on case series that may be affected by publication bias . in conclusion ,
our case report adds new evidence on the feasibility , safety , and efficacy of clina .
further studies are needed to clarify if transcranial ultrasound or other modalities such as mr and/or ct perfusion are able to early select which patients are likely to profit from clina .
 vasospasm ( vsp ) is one of the major causes for prolonged neurologic deficit in patients with aneurysmal subarachnoid hemorrhage . 
 few case series have reported about continuous local intra - arterial nimodipine administration ( clina ) in refractory vsp . 
 we report our experience with clina in a patient with refractory cerebral vsp . 
Introduction
Case Report
Discussion