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Nevrologiya Jumali
(Elmi-praktik jurnal)National Journal o f Neurology
(Scientific-practical journal)HauuoHaibHbm >KypHai HeBpoiomu (HayvHO-npaKmuHecKuu MypHan)
Milli Ncvrologiya Jurnali, 2014 Ns 2 (6), 27-31
CORRECTION OF NON-MOTOR VEGETATIVE FLUCTUATIONS
WITH PARKINSON'S DISEASE BASED ON LEVODOPA TREATMENT
•T a ry a n y k F..A., PhD
Ukrainian Medical Dental Academy, Poltava. Ukraine
Abstract
The influence of dopamine receptor agonists in the Iransdermal and oral forms of drugs and amantadine for a non-motor autonomic fluctuations of patients with different duration of the disease during the treatment of Parkinson's in a stable dose of levodopa were established. It was analysed, that the use of dopamine receptor agonists in the iransdermal and oral forms of drugs reduce the frequency and duration of vegetative non-motor fluctuations of patients with Parkinson's disease. The use of amantadine sulphate has little effect in a decrease of non-motor autonomic fluctuations.
Key words: Parkinson's disease, non-motor fluctuations, lcvodopathcrapy. P a rk in so n ’s disease - is a steadily progressive
n eu ro d eg cn crativ c disease ch aracterized by a g rad u al increase in m o to r, m ental an d a u to n o m ic disorders.
But despite the advances in th e treatm en t o f the disease, it retains a progressive course and inevitably leads to disability o f p atien ts [1,2],
A s the disease progresses in its clinical picture n o n -m o to r m an ifestatio n s are getting increasing ly im p o rta n t, w hich can largely affect th e quality o f life o f p atien ts an d th eir degree o f disability th a n the classic m o to r sy m ptom s o f P ark in so n ’s disease [2-5].
N o n -m o to r flu ctu atio n s arise m ainly during th e "off" tim e a n d decrease o r d isap p ear after levodopa ad m in istratio n . A ll n o n -m o to r sym p tom s th a t occur w ith different phases o f levodo pa actio n are divided in to the follow ing groups: vegetative, m ental an d sensory. Vegetative fluc tu atio n s d o m in ate in the clinical picture o f n o n m o to r sym ptom s [1-4,6-9], T he app earan ce o f th e flu ctu atio n s depends on the severity an d d u ra tio n o f the disease stage a t H oen an d Y ah r, the d u ra tio n o f use an d the dose o f levodopa [5,6,8- 10], W hen disease onset early fluctuations ap p ear faster an d are p ro n o u n ced . Som e role o f gender factors: w om en's a u to n o m ic flu ctu atio n s are o b serv ed m o re fre q u e n tly th a n m en’s ones [2,9,10],
N o n -m o to r m anifestations m ay o u tp ace the developm ent o f the disease an d m o to r w orsem - ing m ay persist afte r the reduction o f sym ptom s o f Parkinson's disease. T his is explained by the involvem ent o f the basal ganglia and closely related limbic, diencephalic, brainstem struc- • • c-mail: tkapol@mail.ru
lures, th e fro n tal co rtex [2,7-12], T h e ap p ro ach es to tre a tm e n t o f n o n -m o to r flu ctu atio n s a rc n o t well developed, b u t sh o u ld be based on the sam e principles as the c o rre c tio n o f m o to r flu ctu a tions. Ft is im p o rta n t to establish clearly in w hich phase o f certain sy m p to m s a p p e a r [2,5-9].
The aim o f o u r stu d y w as to investigate the influence o f d o p a m in e re c e p to r agonists in the tran sd erm al a n d o ral form s o f d ru g s an d a m a n tadine on n o n -m o to r a u to n o m ic flu ctu atio n s o f patients w ith a d ifferent d u ra tio n o f the disease d uring the treatm en t o f P ark in so n 's is a stab le dose o f levodopa.
M a te ria l and m ethods. W e ex am in ed 30 patients (20 w om en a n d 10 m en) w ith an ak in e tic-trem or form o f P a rk in so n ’s disease w ho w ere treated in the neurology d ep a rtm e n t o f Poltava R egional C linical H o sp ital by N .V .Sklifosovsky and observed in the cen te r o f P ark in so n a t the D ep artm en t o f N erv o u s D iseases w ith n eu ro surgery an d m edical genetics H S E E U "U k rai nian M edical D ental A cadem y". D iagnosis w as m ade according to the sta n d a rd o f the In ter natio n al C lassification o f D iseases o f the X revi sion. T h e v erific atio n o f th e d iag n o sis o f P arkinson's disease w as carried ou t according to the in tern atio n al clinical diagnostic criteria o f the Bank o f the b rain o f P ark in so n ’s D isease Society o f G re a t Britain. T he severity o f disease was d eterm ined by th e ratin g scale U nified Parkinson's D isease R atin g (U P D R S ).
T he average age was 60.5±10.8 years. The average d u ra tio n o f disease - 10.9±4.5 years. T he stage o f the disease w as evaluated on a scale H oen an d Y ahr. T he ratin g vegetative state o f
patients was conducted by a questionnaire to assess autonom ic functions. The quality o f life o f patients was determined by PDQ-39 scale. All patients received continuous therapy with lev- odopa drugs 4 times a day (daily dose o f lev- odopa was 375-500 mg). The disease severity on a scale Hoen and Y ahr was - 3.5±0.5.
By the m ethod o f the treatm ent, patients were divided into three groups: group 1(10 patients) - the duration o f receiving levodopa 7.3+1.5 years - received rotigotine as a transderm al patch in the form o f "Neupro" 8 mg 1 time a day for 3 weeks; group 2 (10 patients), the duration of receiving levodopa 6.6±1.4 years - pramipexole as a drug "Pramipex" 1.5 mg per day for three divided doses for 3 weeks (after gradual, within 3 weeks o f titration dose); group 3 (10 patients),
the duration o f treatm ent with levodopa 4.311.6 years - received am antadine sulfate oral dose of 300 mg a day in three divided doses for 3 weeks. The control group - 10 patients (4 W'omen and 6 men), d u ra tio n o f treatm en t w ith levodopa 5.211.8 years, which were treated only by lev odopa 4 times a day (the duration o f receiving levodopa 3.110.9 years).
The general clinical, neurological and neu ropsychological exam ination was carried out for all patients at the beginning and end o f treat ment. The patients kept diaries to assess periods o f activation, deactivation, and appearances non-m otor fluctuations o f throughout the study.
Results and discussion. Features o f autonom ic disorders were evaluated on a scale o f U PD RS. Autonomic fluctuations are shown in Table 1.
Table 1 Patient's basic autonomic disfunction with Parkinson's disease at the beginning of treatment (%)
Signs 1 group (n~10) 11 group (n= 10) 111 group (n=10) Control (n=10) Hyperhydrosis 60 55 55 50 Feeling hot/cold 20 10 10 20 Hypersalivation 40 50 50 30 Abdominal discomfort 20 30 20 20 Frequent urination/dysuria/incontinence 50 30 30 30 Sexual dysfunctions 40 35 40 20 Orthostatic hypotension 10 5 10 10 Dyspnea/compulsive cough 20 10 30 20 Constipation 70 60 60 70 Table 2 The emergence of non-motor symptoms of autonomic in the action phase of levodopa (*/•)
Signs I group (n=10) 11 group (n=10) III group _____ (n=10) Control (n=10) Period «on» Period «off» Period «on» Period «off>> Period «on» Period «off>> Period «on» Period «ofT» Hyperhydrosis 10 50 20 40 20 50 30 60 Feeling hot/cold 10 40 20 30 10 40 10 40 Hypersalivation 20 50 30 40 20 50 40 60 Abdominal discomfort 20 30 10 40 20 50 10 30 Frequent urination/dysuria/ incontinence 20 60 10 40 20 30 10 50 Orthostatic hypotension 10 20 10 30 20 20 10 10
The highest frequency of autonomic disorders observed in all three groups of women and was pre sented in the form of constipation, dysurinational dis orders, hyperhidrosis, hypersalivation. The non motor autonomic dysfunctions are more pronounced during the "off' action of levodopa. Sometimes bipha- sic fluctuations are observed (Table 2.).
Y ou can see from the table 2 the m ost fre quent autonom ic fluctuations appeared in "o ff' period: sw eating (50% o f the off period in the first group and 60% - in the second group of patients), salivation (50% in the first and second groups during the 60% o ff - in the control group
o f patients), the feeling h o t and cold, urinary dis orders. H ypcsalivation can indirectly be attrib uted to the n o n -m o to r autonom ic sym ptom s, because it depends o f directly on swallowing function. H ow ever, a proved stim ulating effect o f levodopa on saliva production.
T he rare vegetative m anifestations include: abdom inal discom fort, o rth o static hypotension, nausea, respiratory function as breathlessness, chest's discom fort o r com pulsive cough. In the course o f the study, after treatm ent in groups o f patients there were changes in autonom ic m ani festations fluctuations (Table 3).
Table 3 P atien t's basic autonomic disfunction with Parkinson's disease at the beginning of treatm ent (%)
Signs 1 group (n=10) 11 group (n=10) III group (n=10) Control (n=10) Period «off» Period «off» Period «off» Period «off» Hyprehydrosis 30* 10* 30* 60 Feelings hot/cold 40 10* 30 40 Hypersalivation 40 20 40 60 Abdominal discomfort 10 20 40 30 Frequent urination/dysuria/ incontinence 20* 20 30* 50 Orthostatic hypotension 40* 10 10 10
Note: * - p<0.05 - compared with the group of patients before and after treatment.
After treatm ent there was a positive effect as a Conclusion. Thus, as a result o f studies, the decrease in non-m otor vegetative symptoms in positive results obtained in the form o f reducing groups, treated with rotigotine and pramipaxole. the frequency and duration o f vegetative non- In the first group o f patients, who were treated m otor fluctuations o f patients with Parkinson's with rotigotine, an increased incidence of ortosta- disease. It’s found that the use for rotigotine has tic hypotension was noticed, but cases o f hypoten- a positive effect, but it is desirable to use in the sion were observed in other groups o f patients, elderly and young people with Parkinson disease M ost likely a sym ptom of the advanced stage o f in the absence o f orthostatic hypotension and the disease o f older patients. However, the pres- allergic reactions in anamnesis,
ence o f orthostatic hypotension may be due to the Using am antadine sulphate has little effect, am plification o f dopam inergic therapy (dopam ine com pared to the efTect on levodopa-induced receptor agonists). Some patients had cutaneous m otor dyskinesia. The application of a dopam ine m anifestations in the form o f itching, redness at receptor agonist in the form o f a transderm al the place o f transderm al patch application. patch and oral drugs in average therapeutic dose
The positive results were found in groups o f (1.5 mg) has a positive efTect and may be rccom- patients treated with pram ipcxolc and am anta- mended for the non-m otor vegetative fluctua- dine sulfate M ore rapid effect was observed lions correction for Parkinson’s disease patients w h e n pram ipcxolc was used at a dose o f 1.5 mg on the base o f levodopa treatm ent in a stable per day (the second group o f patients). dose.
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