trigeminal neuralgia ( tn ) is a debilitating pain syndrome that is characterized by agonizing , paroxysmal , and lancinating pain .
the recommended first - line treatment for tn is medical therapy , but this often fails to provide pain relief .
thus , second - line treatment modalities are given to patients whose symptoms are intractable or who can not tolerate medication .
these treatment modalities include invasive procedures such as microvascular decompression ( mvd ) , and ablative procedures such as gamma knife radiosurgery ( gkrs ) , percutaneous balloon microcompression , radiofrequency rhizotomy , and glycerol rhizolysis .
recently , gkrs has been used as a treatment modality in several centers for patients with concurrent medical illness who are poor candidates for mvd or who refuse more invasive surgery17,20 ) .
other treatment modalities provide short - term pain relief at a rate of 80 - 90% ; gkrs also produces short - term alleviation of pain at similar rates , usually within 6 - 12 months after the operation2,3,7,9,11,15,18,23,29 - 31 ) . pain relief after mvd and radiofrequency rhizotomy for long - term periods has been well reported . in previous studies ,
patients who underwent mvd and radiofrequency reported favorable long - term pain relief of for more than 5 years1,5,10,25,28,32 ) .
however , long - term outcomes of gkrs for tn have been published in only a few reports12,22,29 ) .
thus , we conducted the present study to analyze the long - term outcomes in a series of patients with tn who underwent single gkrs treatment and were followed up for a minimum of 60 months .
between march 1995 and march 2009 , 40 patients with typical tn underwent gkrs at our clinic .
indications for gkrs included medically intractable pain , > 65 years of age , refusal of invasive procedures , or failure of previous invasive procedures . among them , we retrospectively reviewed the medical records of patients with tn undergoing gkrs treatment that had a minimum follow - up of 60 months .
patient demographic characteristics , clinical presentation , treatment history , and the radiosurgical modality were reviewed in 22 patients whose median follow - up was 92.2 months ( range : 60 - 144 months ) .
all patients were treated with leksell gamma knife ( eleckta instruments , stockholm , sweden ) under local anesthesia . as a planning tool ,
the kula system was used until 2001 , and the leksell gamma plan system ( eleckta ab , stockholm , sweden ) has been used since 2001 .
all patients were treated using a single isocenter through a 4-mm collimator helmet targeting the root entry zone of the trigeminal nerve ( fig .
the mean maximal dose to the target was 77.1 gy ( range , 65.2 - 83.6 gy ) .
long - term outcomes were established by face to face interview with a written questionnaire after the treatment in the outpatient clinic .
the questionnaire was devised based on the barrow neurological institute ( bni ) pain scale24 ) but modified at our institution to better incorporate the use of adjuvant medications .
facial pain outcomes were categorized into one of the following classes : grade i , no pain , no medication ; grade ii , no pain with medication ; grade iii , > 50% improved pain with medication ; grade iv , 50% improved pain with medication ; and grade v , no pain relief .
patients with grade i - ii on the pain scale ( equivalent to bni grades i and iiia ) were considered to have a good treatment outcome .
patients with grade iv - v on the pain scale ( equivalent to bni grades iv and v ) were considered to have a poor treatment outcome ( table 1 ) .
statistical verification was determined using spss statistic software , version 13.0 ( spss , inc .
the mean age was 61.5 years ( range 25 - 84 years ) , and the mean symptom duration from onset to treatment was 46.8 months ( range 1 - 84 months ) .
the most common distribution of pain involved the second and third divisions of the trigeminal nerve , observed in a total of 40.9% of patients ( 9 out of 22 patients ) .
thirteen patients had right - sided pain , and 9 had left - sided pain . during the last follow - up period ,
6 patients ( 27.3% ) had good treatment outcomes ( represented by grades i and ii ) , and 7 patients ( 31.8% ) had poor treatment outcomes ( represented by grades iv and v ) during a median follow - up period of 92.2 months ( range 60 - 144 months )
. of the 6 patients with good outcomes , 4 patients ( 18.2% ) experienced complete pain relief without medication , and 2 ( 9.1% ) had complete pain relief with medications .
of the 7 patients with poor outcomes , 5 patients ( 22.7% ) experienced 50% improved pain with medication , and 2 ( 9.1% ) had no pain relief ( table 3 ) . subgroup analysis of excellent , good , and poor outcomes found 2 statistically significant factors related to achieving and maintaining complete pain relief : symptomatic periods before treatment ( p=0.035 ) and previous surgery ( p=0.008 ) .
however , sex , age , pain distribution , and laterality of pain did not correlate with facial pain improvement ( table 4 ) . out of a total of 22 patients ,
16 patients had been treated with medication only before gkrs ( primary group ) , and 6 had gone through mvd prior to gkrs ( secondary group ) . during the final follow - up period ,
patients with good outcomes were 37.5% and 0% in the primary and secondary group , respectively ; patients with poor outcomes , on the other hand , were 12.5% and 83.3% in the primary and secondary group , respectively ( table 5 ) .
of the 22 patients , only one patient ( 4.54% ) experienced facial numbness after gkrs , with grade iii pain on the pain scale .
none of the patients had neuropathic pain , dry eye , keratitis , or jaw weakness after gkrs .
tn patients in whom medical therapy fails are recommended to undergo several treatment modalities , including mvd , radiofrequency rhizotomy , percutaneous balloon microcompression and gkrs . in general ,
the most effective surgical treatment is considered to be mvd in healthy patients because it has a demonstrated effective initial pain - free rate and good long - term outcomes .
barker et al.1 ) reported that the pain - free rate was maintained at 70% of 1185 patients for a median of 6.2 years after mvd .
severe complications that developed include 2 deaths ( 0.2% ) and 16 patients ( 1% ) with ipsilateral hearing loss .
tronnier et al.27 ) reported that 65% of patients had excellent outcomes at 10 years , and 63% at 20 years after mvd . in this study ,
broggi et al.4 ) reported that 53 - 94% of mvd patients were pain - free after a long - term follow - up .
they also reported that the mortality of mvd was 0.3% and that cranial nerve dysfunction rates ranged from 0.1 - 3% .
additionally , radiofrequency rhizotomy also demonstrated an effective long - term outcome for tn patients .
taha et al.26 ) found that 75% were pain - free at 10 years , and 23% experienced facial dysesthesia . in previous studies ,
patients who underwent mvd reported long - term pain relief at rates of 62 - 89% , and patients who underwent radiofrequency reported long - term pain relief at rates of 20 - 82% for > 5 years after achieving a short - term pain relief rate of > 90%1,4,5,10,25 - 28,32 ) .
however , severe complications have occurred in tn patients who underwent mvd or radiofrequency rhizotomy at rates of approximately 2 - 19%1,4,5,10,25 - 28,32 ) . in previous reports with long - term follow - up , gkrs for tn patients
has long term outcomes slightly inferior to mvd and radiofrequency rhizotomy , but with lower complication rates .
urgosik et al.29 ) reported that 80% of 107 patients had good outcomes ( patients with 60% < residual pain ) at a median of 5 years .
little et al.12 ) reported that 83% of 136 patients had good outcomes ( bni pain score of class i , ii , or iii ) at a median of 6.3 years .
riesenburger et al.22 ) reported that 58.5% achieved good outcomes ( bni pain score of class i , ii , or iii ) at a follow - up period of 48 months .
these reports have demonstrated that gkrs is a safe technique for the management of tn , as trigeminal sensory disturbance , the main complication of radiosurgery for tn , only developed in approximately 10% of the patients .
in addition , gkrs patients did not develop any of the severe complications which patients that had undergone mvd or radiofrequency rhizotomy experienced14 ) .
however , most of the other reports on gkrs and tn combined the longer - term follow - up patients with more recently treated patients , thus making it more difficult to identify long - term results . in the present study ,
we strictly evaluated long - term outcomes at a follow - up period of a minimum of 5 years .
thus , our data demonstrate that patients experience lasting pain relief with few complications after gkrs , although patients with good outcomes are fewer than in the previous long - term follow - up studies of outcomes after gkrs .
this seems to be due to the fact that only patients with no pain regardless of medication were included in the " good outcome " patient group in our study , whereas published reports on long - term follow - up studies on gkrs included patients with medication - controlled pain in the " good outcome " group .
because pain negatively impacts upon the quality of life of chronic tn patients , we think that the goal of treatment in tn should be complete pain relief . therefore , we believe it is better to grade patient outcome by the reporting of pain - free outcomes that clearly separates effective pain relief from continued pain . in the current study , patients with pain that had decreased by 50% or more with the use of medication were classified separately as patients with fair outcomes . as a result
, our data demonstrated that patients with good and fair outcomes comprise 72.7% of all treated patients , which is a similar outcome to that in previous reports .
therefore , from the results of this 5-year long - term follow - up study , we suggest that the proportion of patients with good outcomes , consisting purely of pain - free patients with or without medication , after gkrs was 27.3% .
published reports have used radiation dose protocols ranging from 70 - 100 gy7,8,21,31 ) . in general , higher doses of radiation are related to better outcomes , but complications , including facial sensory loss and paresthesia , increase at doses greater than 90 gy19,21 ) . generally , maximal radiation doses between 70 - 90 gy are used to treat tn . in previous long - term follow - up studies ,
the mean maximal radiation dose was approximately 80 gy , and complications included facial numbness , which affected approximately 10% of the treated patients12,22,29 ) .
in the present study , the mean maximal dose was 77.7 gy , which is lower than that utilized in other recent studies ; this is partly due to the long follow - up period which started from 1995 , and partly because the dose was slightly lowered to avoid the development of lasting complications . in our study , only one patient ( 4.54% ) experienced facial dysesthesia . thus , we believe that lower radiation doses are associated with lower complication rates .
the presence of previous surgery is regarded as a predictive factor significantly associated with a poor short - term outcome6,13,16,20 ) .
however , long - term pain relief factors have not been well studied until recently .
little et al.12 ) recently reported that at long term follow - up , 75% of patients who were treated with primary
gkrs achieved long - term pain relief at 7 years , but only 10% of patients in whom previous surgery had achieved a similar outcome .
similarly , our study found that good outcomes in primary gkrs group ( 37.5% ) was better than in secondary gkrs group ( 0% ) , respectively .
also , the presence of previous surgery was observed to be a statistically significant factor related to achieving and maintaining complete pain relief according to our subgroup analysis of good and poor outcomes . based upon these findings
, we have come to believe that there is significant correlation between previous surgery and poor long - term outcomes .
first , although the pain intensity scale is validated tools for the quantification of pain , they are subjective outcome measures because they are dependent on personal interpretations and variation .
second , the small sample size and retrospective study design limit the power of our outcome observations .
gkrs performed at lower radiation doses not only decreased complication rates , but also lessened the development of more severe complications in the long run
. however , the long - term results of gkrs for tn are not as satisfactory as those of mvd and other conventional modalities .
although gkrs achieves relatively good outcomes of initial pain relief , our results suggest a steady rate of late failure , particularly among patients who performed secondary gkrs following prior surgery .
gkrs is a safe , effective and minimally invasive treatment modality for only limited group of patients who are not suited to more invasive treatment .
 objectivegamma knife radiosurgery ( gkrs ) is the least invasive surgical option for patients with trigeminal neuralgia ( tn ) . 
 however , the indications and long term outcomes of gkrs are still controversial . 
 additionally , a series with uniform long - term follow - up data for all patients has been lacking . in the present study , 
 the authors analyzed long - term outcomes in a series of patients with tn who underwent a single gkrs treatment followed by a minimum follow - up of 60 months.methodsfrom 1994 to 2009 , 40 consecutive patients with typical , intractable tn received gkrs . among these 
 , 22 patients were followed for > 60 months . 
 the mean maximum radiation dose was 77.1 gy ( 65.2 - 83.6 gy ) , and the 4 mm collimator was used to target the radiation to the root entry zone.resultsthe mean age was 61.5 years ( 25 - 84 years ) . 
 the mean follow - up period was 92.2 months ( 60 - 144 months ) . according to the pain intensity scale in the last follow - up , 6 cases were grades i - 
 ii ( pain - free with or without medication ; 27.3% ) and 7 cases were grade iv - v ( < 50% pain relief with medication or no pain relief ; 31.8% ) . 
 there was 1 case ( facial dysesthesia ) with post - operative complications ( 4.54%).conclusionthe long - term results of gkrs for tn are not as satisfactory as those of microvascular decompression and other conventional modalities , but gkrs is a safe , effective and minimally invasive technique which might be considered a first - line therapy for a limited group of patients for whom a more invasive kind of treatment is unsuitable . 