Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
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Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : September | Volume : 17 | Issue : 9 | Page : OC05 - OC09 Full Version

Minimal Unified Wilson’s Disease Rating Scale (M-UWDRS) Score Compared to UWDRS Neurological Subscore in Wilson’s Disease: A Cross-sectional Study


Published: September 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/62092.18375
M Mishra, SD Nayak, AK Mallick, BD More, G Mohanty, M Samanta, AK Sahu

1. Senior Resident, Department of Neurology, Srirama Chandra Bhanja Medical College, Cuttack, Odisha, India. 2. Associate Professor, Department of Neurology, MKCG Medical College, Berhampur, Odisha, India. 3. Professor, Department of Neurology, Srirama Chandra Bhanja Medical College, Cuttack, Odisha, India. 4. Associate Professor, Department of Pharmacology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India. 5. Professor, Department of Neurology, Srirama Chandra Bhanja Medical College, Cuttack, Odisha, India. 6. Assistant Professor, Department of Neurology, Srirama Chandra Bhanja Medical College, Cuttack, Odisha, India. 7. Assistant Professor, Department of Neurology, Srirama Chandra Bhanja Medical College, Cuttack, Odisha, India.

Correspondence Address :
Dr. BD More,
Associate Professor, Department of Pharmacology, Mahatma Gandhi Medical College and Research Institute, Puducherry-607402, India.
E-mail: drbdmore@gmail.com

Abstract

Introduction: Wilson’s Disease (WD) is a copper metabolic disorder that affects the nervous system and liver. The Unified Wilson’s Disease Rating Scale (UWDRS) is used for diagnosing WD, but it is time-consuming. Therefore, a less exhaustive scale is needed as a screening tool, such as the minimal Unified Wilson’s Disease Rating Scale (M-UWDRS).

Aim: To evaluate the utility of M-UWDRS in assessing signs and symptoms associated with WD and compare it with the UWDRS (Neurological) subscore.

Materials and Methods: This prospective, observational, non interventional, cross-sectional study was conducted in the Department of Neurology, Srirama Chandra Bhanja Medical College and Hospital, Cuttack, Odisha, India from November 2017 to October 2020. A total of 42 patients with WD, based on the European Association for the Study of the Liver (EASL) guidelines, were enrolled. They were assessed using both M-UWDRS and UWDRS (Neurological) scoring before treatment and at a three-month follow-up.

Results: A total of 42 cases were enrolled, of which 28 were males and 14 were females. The mean age of presentation was 15.4±5.1 years. Both the neurological subscore of UWDRS and M-UWDRS were used pre and post-treatment, revealing a significant improvement in the majority of subjects. Both scores fared similarly in predicting disease severity, treatment outcome, and follow-up. The score of the “minimal UWDRS” correlated with the scores of the UWDRS for neurological subscores (r value: 0.6, p-value<0.001).

Conclusion: M-UWDRS is a user-friendly, quick, and practical prescreening scoring scale for evaluating disorder severity and quantification of the outcomes in comparison to the UWDRS score, especially in resource-constrained and busy neurology departments. Scoring in WD will help in better prognostication of the disease.

Keywords

Copper, Hepatic symptoms, Progressive lenticular degeneration, Psychiatric symptoms

The WD is an inherited autosomal recessive condition associated with mutations in the ATP7B gene, which encodes a transmembrane copper-transporting ATPase, leading to derangement in copper metabolism. The prevalence of WD is 1:30,000-1:50,000 in the Americas, European countries, and the Asian region. Population-based data demonstrate that the genetic prevalence is 3-4 times higher than clinically based estimates (1). According to the World Health Organisation, the worldwide prevalence of WD is 1/10,000 to 1/30,000. The prevalence in Asian countries other than India varies between 33 and 68 per 100,000. There is no Indian community-based prevalence data available, but WD is more common where consanguinity is prevalent (South India) (2).

Mutations in the ATP7B gene and inactivation of the ATP7B transporter result in failure of biliary copper excretion, resulting in copper deposition in body organs, predominantly in the liver and brain (3). Patients with WD present differently, and it remains unclear why some of them present with hepatic symptoms while others present with neurological, psychiatric, or combined symptoms (4). Hepatic disease can be the clinical manifestation (40-60%) of WD, ranging from asymptomatic subjects with slightly elevated hepatic enzymes to cirrhosis or acute liver failure (5). The presentation can vary with age, gender, and duration of untreated copper overload.

Neurological symptoms include several motor dysfunctions associated with abnormalities of the basal ganglia and the cerebellum abnormities. They present as tremor, rigidity, dyskinesia, dystonia, ataxia, chorea, swallowing difficulties, dysarthria, or sialorrhoea. Various psychiatric symptoms have been found, such as attention problems, decreased concentration span, and behavioural issues, along with changes in personality, sadness, and neurosis (3). The intensity of these symptoms has an adverse impact on Activities of Daily Living (ADL).

The aetiology of WD may be multifactorial, involving a combination of genetic, epigenetic, hormonal, and environmental factors. Timely identification of the disease and individualised therapy are critical to prevent the development of illness and resultant cirrhosis or hepatic failure (6),(7). The available laboratory tests are not perfect or specific for WD, as characteristic medical symptoms may not be present in a significant proportion of individuals. Therefore, a comprehensive, standardised, and practical clinical rating scale is essential for monitoring individual treatment responses in routine clinical settings and for utility as a valid endpoint in clinical trials evaluating different interventions (8).

At present, two clinical rating scales are used for the assessment of WD, namely the UWDRS and the Global Assessment Scale for WD (GAS for WD). In 2007, Czlonkowska A et al., reported the UWDRS scale, which reflects the extent of neurological impairment (9). A year later, Leinweber B et al., extended the UWDRS scale by adding hepatic and psychiatric subscales. Currently, the UWDRS consists of three subscales: neurological, hepatic, and psychiatric (10). In 2009, Aggarwal A et al., proposed the GAS for WD, which significantly takes less time compared to the UWDRS. It is composed of two tiers: scoring global disability (Tier 1) and neurological dysfunction (Tier 2) (11). Both rating scales require a relatively long duration to complete the clinical assessment, making it difficult in daily practice. Moreover, they require two to three different medical specialists i.e., a neurologist, gastroenterologist, and psychiatrist for assessment (4).

To reduce the time required, a modified “minimal UWDRS” was proposed as a prescreening tool for use outside scientific trials. The initial nine items of the UWDRS neurological subscale were used to develop a minimal neurological subscale, considered as the “minimal UWDRS.” This abridged scoring scale serves as a questionnaire, with items reported by the patient or their family, allowing the score to be evaluated before the consultation with the treating neurologist (which typically takes 2 to 4 weeks) (12). The utility of this scale has not been previously studied in an Indian set-up like our institution. Therefore, this cross-sectional study was carried out with the primary objective of determining the utility of M-UWDRS in assessment of clinical radiological features in WD and compare it with the UWDRS (Neurological) subscore. The other objectives include estimating the hospital-based incidence of neurological manifestations of WD.

Material and Methods

A hospital-based, non international, observational, prospective, cross-sectional study was carried out at Department of Neurology , SCB, Medical College and Hospital in Cuttack, Odisha, India from November 2017 to October 2020, over a period of three years. The study was carried out after obtaining protocol approval from the Institutional Ethics Committee (IEC) (898/14.08.2017).

Inclusion criteria: Patients aged >8 years who were admitted with clinical features of neurological manifestations of WD in the neurology department at SCB Medical College were further evaluated for WD based on the EASL criteria (Table/Fig 1) (8). Those who were diagnosed with WD and provided written consent were enrolled in the study. In the case of children and adolescent patients, consent was obtained from their parents or legal guardians in writing.

Exclusion criteria: Patients treated on an outpatient basis were excluded from the study. Patients with suspected neuro-WD who fell into the probable category of the EASL criteria, as well as those with any chronic liver disease, history of birth asphyxia, global developmental delay, and substance abuse, were also excluded from the study.

Sample size: As a pilot study, a sample size of 42 patients was selected.

Parameters studied: All epidemiological and clinical parameters, along with patient history, were recorded in a prestructured case record form. Patient demographic details, age at assessment, and treatment at assessment were collected.

The penicillamine challenge test, which involves copper estimation after a penicillamine challenge, was performed on patients as needed. This test has significant value in the identification of WD (12). The penicillamine challenge involved administering a 500 mg dose of penicillamine (irrespective of body weight) at the start of a 24-hour urine collection, which was repeated at 12 hours. Copper excretion in urine of >1600 μg per 24 hours (>25 micromol) is commonly observed in WD compared to other types of liver disease.

Neurological UWDRS and minimal UWDRS were performed before treatment. The full UWDRS, with a maximum score of 320 points, comprises of three subscales representing the major characteristics of clinical expression in WD (Table/Fig 2).

Among the 55 items in the scale, the patient responds to 26 questions, while the physician scores 29 items. Each item is scored on a rising 5-point scale, with a score of 0 indicating no symptoms and a score of 4 indicating the worst possible characteristic (9),(10).

The “minimal UWDRS”:

The initial 9 items of the UWDRS neurological subscale were used to construct the minimal neurological subscale, which is referred to as the “minimal UWDRS” (4). Since this reduced rating scale consists solely of a questionnaire where the items are reported by the patient or their family (usually referring to the previous two to four weeks), the resulting score can be assessed before the consultation with the treating physician. The items used in the minimal UWDRS are as follows:

- Mobility
- Falling
- Salivation
- Swallowing
- Feeding
- Dressing
- Taking a bath or shower
- Grooming
- Toilet use

Except for items 3 and 4, all other items evaluate the degree of independence for Activities of Daily Living (ADL) (4).

Treatment was done according to the recent WD: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Paediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India (13). Rescoring was done on follow-up after three months.

The study cohort was classified into three severity groups by the authors based on the scores. Patients with scores of 0-12 were classified as mild, those with scores of 13-24 were classified as moderate, and those with scores of 25-36 were classified as severe. The post-treatment outcome was categorised as good improvement or mild improvement. Good improvement was defined as a decrease in score of nine points or reaching a minimal (0) score after treatment. As there are nine categories, it was postulated by the authors after discussion with experts that a decrease in score of nine would reflect an improvement in ADL. A decrease in score of less than nine was considered a mild improvement. These cut-offs were considered for the present study only by the authors after discussion with experts.

Statistical Analysis

Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) Software version 21.0 with the help of a departmental statistician. The score of the “minimal UWDRS” was correlated with the scores of the UWDRS for neurological subscores. A correlation coefficient (r) of less than 0.5 and a p-value <0.05 were considered statistically significant.

Results

A total of 42 cases were included in the study, with 28 being males and 14 being females. The mean age of presentation was 15.4±5.1 years (mean±SD). The maximum age observed was 32 years, while the minimum age was 9 years. The mean duration of disease was nine months, and the average length of hospitalisation was 14 days. All patients received treatment with Zinc. Among the patients, 30 (71.43%) were treated with penicillamine, 34 (80.95%) received trihexyphenidyl, 25 (59.53%)were given dopamine, and 23 (54.76%) received antipsychotics. Additionally, 7 (16.7%) of patients were given antiepileptics, and 50% (N=21) received tetrabenazine for symptomatic benefit.

All patients were evaluated using both the M-UWDRS and UWDRS (neurological subscore) before treatment and after three months of follow-up. In the MIN-UWDRS, the mean prescore was 20.29, and the mean post-score was 12.95, with a mean difference of 7.34. This indicates a 36% decrease in the mean score. In the UWDRS (neurological subscore), the mean prescore was 98.29, and the mean post-score was 64.71, with a mean difference of 33.57. This corresponds to a 34% decrease in the mean score (Table/Fig 3). The score of the “minimal UWDRS” was found to be correlated with the scores of the UWDRS for neurological subscores (r=0.6), and a p-value of 0.001 was considered statistically significant.

The comparison percentage of decrease in mean scores between UWDRS (Neurological subscore) and M-UWDRS is summarised in (Table/Fig 4). An easy severity-based classification was performed using the M-UWDRS score. Good improvement was observed in the low-score cohort, with 16 (38.1%) of patients showing significant improvement. Patients in the moderate severity group accounted for 12 (28.6%), and those in the severe severity group accounted for 14 (33.3%). These groups had limitations in disability and a poorer prognosis based on the severity classification using the M-UWDRS score (Table/Fig 5).

Discussion

Epidemiological data on the community-based incidence and prevalence of WD in India is lacking. Most of the available data comes from hospital-based reports. The exact incidence of WD has not been previously documented in any Indian study (14). The NIMHANS WD registry mentions a yearly incidence of 15-20 new cases (2). At SCB Medical College, Cuttack, India, the annual incidence is approximately 10-15 cases. In a study by Yachha SK et al., it was reported that among 235 patients with hepatobiliary spectrum disorders studied over a three-year period, eight patients (7.6%) had WD (15).

The onset of WD symptoms varies widely, but it mostly manifests between the ages of 5 and 35 years (3). In this study, the ages of patients ranged from 9 to 32 years. The reasons for the early age of onset of WD in this series in Eastern India cannot be explained. However, it is possible that certain environmental factors or cooking food in copper vessels may be responsible for triggering WD symptoms. Adult patients with WD are more likely to have liver cirrhosis compared to children (3).

This study found a higher prevalence of WD, with a male to female ratio of 2.1:1, which was similar to the findings of the study by Litwin T et al., (16). Gender appears to have a modifying effect, as females are more likely to present more often with acute liver failure than males. Litwin T et al., reported that liver involvement in WD occurs more frequently in women, and they tend to express neuropsychiatric symptoms almost two years later compared to men. The neuropsychiatric type of WD is expressed at diagnosis in both men and women (16). These differences could be because of due to the protective effect of estrogens and differences in iron metabolism.

Most current WD treatment guidelines recommend the use of chelators to manage symptoms [5,8,13]. The maintenance treatment typically includes zinc, especially at the start of therapy for asymptomatic or presymptomatic individuals. Zinc has been found to be effective and well-tolerated in neurological WD patients. However, caution should be exercised in patients with liver WD because of the due to the potential worsening of liver condition. In this study, all patients received zinc as maintenance therapy. Other medications used included penicillamine, trihexyphenidyl, dopamine, antipsychotics, antiepileptics and tetrabenazine based on individual presenting symptoms. However, the management of neurological WD is faced by therapeutic challenges, especially in individuals with tremors, parkinsonism, and involuntary muscle contractions, which significantly contribute to the UWDRS score (10). It is recommended that initial drug therapy for WD should comprise chelating agents such which D-penicillamine, as was also followed in this study (10).

The UWDRS scale was developed to assess neurological deficits and functional impairment due to the wide heterogeneity and combined neurological symptoms observed in WD. In this study, no significant difference was found in monitoring therapy between the minimal UWDRS score and the UWDRS neurological subscore, which was in concurrence with trends observed in earlier studies (4),(15). Oder W et al., demonstrated a definite correlation between the intensity of neurological dysfunction and restricted functional activity (17). Volpert HM et al., also demonstrated a significant correlation between the “minimal UWDRS” (UWDRS Part II without one item) and total as well as neurological UWDRS scores (4). In clinical practice, the “minimal UWDRS” is a convenient and time-saving screening tool to identify neurological dysfunction in WD patients (4).

The presentation of WD can vary widely in terms of type and severity. The minimal UWDRS can aid in the classification of disease severity. In this study, an easy severity-based classification was conducted using the M-UWDRS score. It was found that patients in the mild group had a good outcome with improvement, while those in the moderate and severe groups had limitations in disability and a poorer prognosis. The typical presentation of WD is observed in adolescents and young adults, but it can manifest at any age. There is significant variations in the neurological abnormalities of WD, both in terms of presentation and severity. These abnormalities are classified into syndrome types based on the predominant symptoms, which include tremor and ataxia, bradykinesia (parkinsonism-like symptoms), and dystonia. However, in many cases, it is difficult to classify the neurological characteristics as patients may have multiple signs and abnormalities, each with varying degrees of intensity (18). The M-UWDRS score can also be used to classify the neurological cohort of WD and serve as a severity scale. Primary care physicians, pediatricians, and nurses can use this score to classify the disease and determine if referral to a higher centre is necessary.

One advantage of the minimal UWDRS scale is that the neurological questionnaire can be filled out by the patient or their caregiver prior to the medical appointment, even in the absence of a neurologist. Additionally, a brief questionnaire can be administered more frequently compared to an extensive neurological evaluation. This can help in self-reflection on disease symptoms, resulting in adherence to the treatment and better outcomes. The physician can quickly assess whether the patient’s ADL are limited by neurological symptoms, as seven out of the nine items in the minimal UWDRS evaluate the level of independence in ADL.

Limitation(s)

There were a few limitations associated with the present study. Firstly, the analysis was based on a relatively small group of 42 patients, which may not allow for meaningful analyses of all subgroups. WD is a rare inherited disorder, so obtaining a large sample size can be challenging. Another limitation was that the neurological subscores of the M-UWDRS were compared with the UWDRS, Therefore, the assessment of hepatic and psychiatric involvement may have been missed.

Conclusion

The “Minimal UWDRS” is a pragmatic, non exhaustive, and cost-effective tool for evaluating the neurological status of WD patients with neurological symptoms. It allows for quantification of outcomes and can be used for prognostication and severity classification. It can be administered by all health professionals and aids in improved follow-up and prognostication. However, further investigations in larger samples of patients are needed to confirm the validity of the Minimal UWDRS and its classification of severity.

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DOI and Others

DOI: 10.7860/JCDR/2023/62092.18375

Date of Submission: Dec 14, 2022
Date of Peer Review: Mar 14, 2023
Date of Acceptance: Jul 26, 2023
Date of Publishing: Sep 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Dec 15, 2022
• Manual Googling: Jun 14, 2023
• iThenticate Software: Jul 22, 2023 (10%)

ETYMOLOGY: Author Origin

EMENDATIONS: 10

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