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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 2  |  Page : 141-144

Nondevice-assisted therapy for advanced Parkinson's disease with severe complications revisited for resource-restricted setup


1 Department of Neurology, Sri Ramakrishna Ashrama Charitable Hospital, Thiruvananthapuram, Kerala, India<, India
2 Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3 Department of Neurology, Government Medical College, Thiruvananthapuram, Kerala, India
4 Department of Paediatric Surgery, Government Medical College, Alappuzha, Kerala, India
5 Department of Neurology, Sri Ramakrishna Ashrama Charitable Hospital, Thiruvananthapuram, Kerala, India

Date of Submission19-May-2020
Date of Decision30-Oct-2020
Date of Acceptance23-Dec-2020
Date of Web Publication18-May-2021

Correspondence Address:
Dr. Chandra Sadanandavalli Retnaswami
Department of Neurology, Sri Ramakrishna Ashrama Charitable Hospital, Sasthamangalam, Thiruvananthapuram
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijhas.IJHAS_119_20

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  Abstract 

INTRODUCTION: A good percentage of patients with parkinsonism land up with moderate-to-severe complications after 5 years of treatment which causes severe disability to patients and caregivers. Device-assisted treatments do not always give consistent results and availability and affordability is also a problem. Therefore, we, in our charitable hospital, tried in six consecutive patients the role of liquid Levodopa Carbidopa Ascorbic acid Solution therapy which is relatively cheap and does not need technical expertise.
MATERIALS AND METHODS: Patients who qualified as primary Parkinsonism and had severe complications as per the UPDR Section IV scoring and were considered unsuitable for device-assisted treatment options for various reasons were included for the study. They were given the LCAS therapy and scores repeated at 7 days and 4–6-month follow-up.
RESULTS: All patients had improved in UPDR IV scores, Everyday Abilities Scale for India, Zarit's score, and GDR. One patient had hyponatremia and all others remained stable at 4–6-month follow-up with 75% or less of their previous dose. All the parameters under dyskinesias and three of four parameters under fluctuations showed sustained improvement with significant P value at 1 week and 4–6 months in all cases.
CONCLUSION
LCAS is an easily accessible, cost effective treatment option which significantly improves quality of life in patients, who are not eligible or cannot afford Deep Brain Stimulation.

Keywords: Idiopathic Parkinsonism, liquid L-dopa, severe motor fluctuations


How to cite this article:
Retnaswami CS, Pai AR, Chithra P, Vidhya Annapoorni C S, Vargese J. Nondevice-assisted therapy for advanced Parkinson's disease with severe complications revisited for resource-restricted setup. Int J Health Allied Sci 2021;10:141-4

How to cite this URL:
Retnaswami CS, Pai AR, Chithra P, Vidhya Annapoorni C S, Vargese J. Nondevice-assisted therapy for advanced Parkinson's disease with severe complications revisited for resource-restricted setup. Int J Health Allied Sci [serial online] 2021 [cited 2021 Jun 17];10:141-4. Available from: https://www.ijhas.in/text.asp?2021/10/2/141/316280




  Introduction Top


Idiopathic  Parkinsonism More Details is a chronic progressive degenerative disease characterized by tremor, rigidity, bradykinesia, and postural instability. Charaka of the 3rd century B.C. described the disease as Vepathu or Kampa vada and the use of Mucuna seed was popular. Mucuna seeds contain natural levodopa that is easily converted to dopamine in the brain, which is the source of L-dopa.[1] Motor fluctuations are common in at least 50% of patients on L-dopa therapy by 5 years.[2] Cotzias, et al. in 1967, reported the effects as well as side effects of chronically administered L-dopa.[3] When patients develop severe complications, the various options available are device-assisted treatments such as deep brain stimulation, subcutaneous apomorphine infusion, and duodenal levodopa infusion. Each option is chosen on an individual basis and has variable benefits.[4],[5] A simple nondevice-assisted technique has been tried in the past, though not very popularly used because of discontinuation due to the need for frequent dosing, dyskinesias, or lack of sufficient on effect in some patients and mentioned as an outdated treatment in the literature.[6] It deserves to be tried in at least some patients who have no accessibility, affordability, other comorbidity-associated contraindications, and cognitive and psychiatric involvement.[7]


  Material and Methods Top


Patients who have been investigated previously and were confirmed by clinical criteria as primary Parkinsons s disease and had severe complications were included for the levadopa carbidopa ascorbic acid therapy (LCAS) after informed consent and consent from the institutional review board. Cross-over study design was used where patients served as their own controls before and after the current treatment. The inclusion criteria were patients on levodopa therapy for at least 5 years with severe complications and either not affordable or unwilling to pursue device assisted treatments in higher centers. Exclusion criteria was; patients having other neurological illnesses complicating Parkinsonism and those unwilling to participate in LCAS therapy. All of them were scored for severity of complications with section IV of Unified Parkinsons Disease Rating scale. Informed consent was obtained and videos recordings were done in patients own smartphone. Family members were asked to either mark in a clock the timings of medications, complications, and any other observations for every 24 h by clock recording by caregiver [Figure 1]. Patients' total dose of L-dopa and other medications were recorded. Drugs which have anti-Parkinson's effect were removed when possible. All patients were admitted at least for 5 days. Liquid preparation made as follows. The dose was calculated at 75% of previous dose or less in one patient who was taking a very high dose, i.e., levadopa equivalent daily dose. An equal amount of ascorbic acid for maintaining acidity and preventing oxidation and L-dopa was powdered made to a paste with a small amount of water and then mixed to make an equivalent of 1 g/1 l and stored at 4°C in the refrigerator. The hourly dose of LCAS was decided based on the wake hours and taken in an upright position as far as possible.[8] This study was approved by the institution's review committee. The scores were applied at 7 days and later during follow-up at monthly intervals for 4 to 6 months. Geriatric depression scale (GDS), Everyday Abilities Scale for India (EASI) for patients, and Zarit's caregiver burden score were used for assessing caregivers.[9],[10],[11]
Figure 1: It shows the sample clock drawing used by caregiver to report response

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  Results Top


Age varied from 49 years to 73 years. There were three males and three females. Drug dose required before LCAS was around 1750mg to 3750 mg, i.e, around 14 to 30 tablets of 125 mg each. Scores at beginning of treatment using UPDR Section IV showed long-duration dyskinesia, severe disability, moderate pain, and significant early morning dyskinesia. The fluctuations showed significant unpredictable off, sudden off, and off while walking. P value was calculated for various categories of complications pre and post treatment at 7 days and 4–6 months.

All these parameters showed sustained improvement at 4–6 months with P value varying from 0.04 to 0.002. The details are shown in [Table 1]. Other complaints were not significant. One patient developed symptomatic hyponatremia which was corrected by fluid restriction. GDS score showed severe depression in two patients and moderate depression in four patients. EASI score showed severe impairment in four cases and moderate in two cases. ZARIT score (which assesses caregiver burden) before LCAS showed severe burden in 4 cases and moderate burden in 2 cases. GDS, EASI, and ZARIT scores in all cases improved to moderate during follow-up. The raw data are depicted in [Table 2] [Video 1 shows a sample patient before treatment LCAS and Video 2 after treatment].
Table 1: The P value of various parameters of section IV UPDR*

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Table 2: Depicts the raw data*

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  Discussion Top


Levadopa carbidopa combination is used as a therapy for patients with idiopathic parkinsonism. It becomes converted to dopamine in the brain. Alkaline environment inhibits absorption and adding acidic substance facilitates absorption and prevents oxidation. The liquid form is likely to facilitate absorption by increased surface area, better absorption, and uniformity in distribution. The problems experienced are cumbersome preparation causing caregiver stress, a difficulty with hourly medication. One patient became drowsy due to hyponatremia. This is known to happen due to increased water intake and tendency of L-dopa to induce ADH secretion.[12] However, there is a very significant improvement in all parameters with reference to dyskinesia and three parameters of fluctuation which started at 1 week of starting therapy and remained sustained in all the patients at 4–6 months follow-up. This considerably improved the EASI and GDS score in patients and Zarit's score in caregiver. Longer follow-up will be needed to assess sustainability and complications. Possibility of shifting over to regular dosages orally will also need to be evaluated during follow-up.


  Conclusion Top


LCAS appears to be of considerable use in patients with severe complications for at least 6 months and significantly reduced caregiver burden and improves EASI and GDS in patients. Therefore, this easy and affordable regime should be tried in all resource-restricted centers even if it gives only short-term benefits.

Limitation

This study was not a controlled study comparing with other device-assisted techniques but a cross-over study. The sample size was small. Follow-up period was only 6 months. Adjuvant drugs used were not uniform in all patients. Blood levels of the drug could not be done as ours is a charitable hospital catering poor patients.

Acknowledgments

We acknowledge with gratitude our patients, their caregivers, and Swami Mokshavratananda, President, Sri Ramakrishna Ashrama Charitable Hospital, Thiruvananthapuram, for all the encouragement.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G. The magic velvet bean of Mucuna pruriens. J Tradit Complement Med 2012;2:331-9.  Back to cited text no. 1
    
2.
Marsden CD, Parkes JD. Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet 1977;1:345-9.  Back to cited text no. 2
    
3.
Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967;276:374-9.  Back to cited text no. 3
    
4.
Yang HJ, Ehm G, Kim YE, Yun JY, Lee WW, Kim A, et al. Liquid levodopa-carbidopa in advanced Parkinson's disease with motor complications. J Neurol Sci 2017;377:6-11.  Back to cited text no. 4
    
5.
Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K, et al. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med 2006;355:896-908.  Back to cited text no. 5
    
6.
Vijiaratnam N, Cheng S, Bertram KL, Williams DR. Liquid levodopa/carbidopa: Old solution, forgotten complication. J Mov Disord 2017;10:164-5.  Back to cited text no. 6
    
7.
Clarke CE, Worth P, Grosset D, Stewart D. Systematic review of apomorphine infusion, levodopa infusion and deep brain stimulation in advanced Parkinson's disease. Parkinsonism Relat Disord 2009;15:728-41.  Back to cited text no. 7
    
8.
Kurth MC, Tetrud JW, Irwin I, Lyness WH, Langston JW. Oral levodopa/carbidopa solution versus tablets in Parkinson's patients with severe fluctuations: A pilot study. Neurology 1993;43:1036-9.  Back to cited text no. 8
    
9.
Yesavage JA. Geriatric depression scale. Psychopharmacol Bull 1988;24:709-11.  Back to cited text no. 9
    
10.
Tripathi R, Kumar K, Bharath S, Marimuthu P, Varghese M. Age, education and gender effects on neuropsychological functions in healthy Indian older adults. Dement Neuropsychol 2014;8:148-54.  Back to cited text no. 10
    
11.
Martin-Carrasco M, Otermin P, Pérez-Camo V, Pujol J, Agüera L, Martín MJ, et al. EDUCA study: Psychometric properties of the Spanish version of the Zarit Caregiver Burden Scale. Aging Ment Health 2010;14:705-11.  Back to cited text no. 11
    
12.
Lammers GJ, Roos RA. Hyponatraemia due to amantadine hydrochloride and L-dopa/carbidopa. Lancet 1993;342:439.  Back to cited text no. 12
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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