Preclinical and Clinical Evaluation of Siravatham (Cerebral Palsy) with Siddha Therapeutic Management in Children

“Special children” is an umbrella term used to classify conditions that childhood disability caused by neuronal damage. The proportion of disabled children in developing countries is generally higher than in developed countries, it is estimated that 6 to 10% of children in India are born disabled. A child who has been determined to require special attention is called as Special Children. Children with multiple disabilities associated with impairments which range across sensory, motor, physical, socio emotional, behavior and cognitive domains known as “Special children” There are many physical disabilities that can affect children. But cerebral palsy is the most common mental disability in childhood. Cerebral palsy is a non progressive disorder of posture and movement often associated with epilepsy and abnormalities of speech, vision and intellect. It results from a defect or lesion of the developing brain. Cerebral palsy occurs in about 1.5 per 1000 live births. Oral Baclofen, Tizanidine, Dantrolene, Diazepam and Gabapentin are widely used for cerebral palsy. Not all patients benefit from this treatment. However this drug was shown to have undesirable other effects such as sedation, respiration problems and muscular weakness, dry mouthl and hallucinations. Patients with localized or multifocal Botulinum toxin injections have risk for antibody formation must be restricted. However, modern drugs can be said to partially fulfill desirable requirements in some extent. It is in the context that we have undertaken a review of the Siddha formulation which could help management of CP. In the view of the above, great efforts have been made to find out the alternate Siddha medicines and methodologies to improve the life style of special children with cerebral palsy. Siddha literature suggested the internal and external therapies which include the Kurunthotti Kudineer, Kollu Podithimirthal and Vasavu Ennai Thokkanam. The history of usage of these medicines and methodologies are very old. In this view, the study was undertaken to evaluate the combined management of internal medicine and external therapies for the management of special children with spastic cerebral palsy. Preclinical studies of Kurunthotti Kudineer: Biochemical analysis: Biochemical Qualitative analysis of trial drug was done in Biochemistry laboratory, Department of Biochemistry, National Institute of Siddha, Chennai. The Bio chemical analysis of trial medicine shows presence of calcium, magnesium, aluminium, sulphate, zinc, alkaloids phenol, hydro quinine and tannic acid. Physicochemical analysis: Physicochemical analysis and Photochemical of Kurunthotti kudineer was done in The Tamil Nadu Dr.MGR Medical University-Chennai. The physicochemical analysis showed the trial drug is in appropriate consistency for trial study In Kurunthotti Kudineer showed Loss of drying at 105C0 was found to be 5.67% it falls in between the limit range (1-20%). so the moisture content shows the good stability of the drug Kurunthotti Kudineer. The total ash in Kurunthotti Kudineer found to be 6.78% and the acid insoluble ash to be 1.53%. The both ash value were under limits. The minimal level of acid insoluble ash shows the less inorganic residue and purity of the Kurunthotti Kudineer. The water soluble extract value of Kurunthotti Kudineer is 12.75% and the Alcohol soluble extractive is 11.48 % its shows the possibility of water soluble constituents such as tannins, sugars, plant acids and mucilage, and alcohol soluble substance such as tannins, resins, and alkaloids to be present in the drug. As the drug Kurunthotti Kudineer having more water soluble constituents than alcohol soluble, it would be non polar. So the trial drug shows good absorption & intracellular distribution without possible of accumulation inside the cells. The good water solubility may rapid the drug absorption and action. Photochemical analysis: Phytochemical of Kurunthotti Kudineer was done in The Tamil Nadu Dr.MGR Medical University-Chennai. The Phytochemical analysis shows the presence of Alkaloids, Quinones. Diterpenes, Flavanoids, Saponin, Carbohydrates. Preclinical safety: Children to get the desired advantage, who must take adequate amount of Kurunthotti Kudineer over a certain length of time, the general opinion that herbal drugs are very safe and the from adverse effects is not true and it can produce undesirable side effects. In our preclinical (NIS/IAEC-IV/07/05012017) acute and 14 days repeated oral toxicity study of Kurunthotti Kudineer showed no mortality of rats up to the higher dose. No behavioural changes or abnormal clinical signs were observed. No treatment related toxicity signs or mortality were observed. The gross necropsy study on the organs showed no abnormal pathological morphology. Clinical Study: The present study was a prospective, open label, non-randomized, outpatient and inpatient based, single centred drug trial conducted in the department of Kuzhanthai Maruthuvam (Paediatric), National institute of Siddha, Chennai. It was conducted during 2016 to December 2018 after obtaining approval from the Institute Ethics Committee (NIS/IEC/2016/11-23/14-10-2016) The trial registered in Clinical trial Registry of India with Reg .No. CTRI/2018/04/013322 was obtained. Single batch of Kurunthotti Kudineer (Internal), Kollu Podithimirthal and Vasavu ennai (External) were prepared for the entire study. The first 30 children with spastic cerebral palsy were screened during the study period. Children of either sex between the age group of 2 to 7yrs, who were diagnosed with spastic cerebral palsy, were identified to include the study. Other type of cerebral palsies and along with seizure disorder, Spinal deformities, impaired vision Autistic Spectrum Disorders, ADD/ADHD (Hyper activity), Mental Retardation, Visual Impairments and Blindness, Hearing Loss and Deafness, Down Syndrome, Spina Bifida, Traumatic Brain Injury were excluded from the study. 30 children satisfied the inclusion criteria and were willing to participate in the study, signed the informed consent. The parents of children who were enrolled was informed about the study, trial drug, possible outcomes and the objectives of the study in the language and terms understandable for them. Children were received internal medicine Kurunthotti Kudineer (2 yrs to 4 yrs - 30 ml, 5 yrs to 7 yrs - 40 ml) twice a day along with external therapies such as massage with Vasavu ennai and Kollu Podithimirthal. Experimental period was 90 days and spasticity was recorded 0th day and followed by every 30th day. Experimental formulations were assigned to each subject and regular study drug reconciliation was performed to document the drug assigned, consumed, and remaining are logged on the drug reconciliation form with sign & date. CLINICAL EFFICACY; The major objective of the work described in this thesis was to elucidate internal medicine Kurunthotti Kudineer alone, combination of internal medicine along with external therapies such as Kollu podithimirthal and Thokkanam compared with positive control routine OPD advice in children with CP influence on assessment of spasticity MAS, MTS muscle tone, Dynamic gait index, Gross Motor Function Classification System (GMFCS), Functional Performance (Disability Assessment Scale), Posture Assessment on upper limb and lower limb assessment of language. In clinical analysis we observed motor function like spasticity, muscle tone, Gross motor function analysis, Gait analysis showed significant improvement in childrens. But the results had shown significantly differed each other. However children had shown significant improvement in all clinical parameters in children. The mean and standard deviation of Kurunthotti kudineer before and after treatment were 4.848 and 3.453 respectively .Which is statistically significant t-value =5.831p value p<0.0001. Statistical analysis reveals that there has been a significant reduction in total scales after treatment indicating the improvement in children doing their daily activities. Statistical analysis reveals that there has been a significant (P< 0.0001) reduction in MAS, MTS, MRCG, GMFCSPAS, DGI, DAS scale after treatment indicating the improvement in children doing their daily activities. The clinical efficacy of the drug was analyzed statistically on all the symptoms mentioned in the assessment criteria. The observation made during the clinical study showed that the trail drug Kurunthotti kudineer (Internal), Kollu Podithimirthal and Vasavu ennai Thokkanam (External) was clinically effective. CONCLUSION: In Siddha literature CP is under the Vatha disease therefore, the therapeutic management is considered to be internal medicine, Kollu podithimirthal and (Thokkanam) massaging. Siddha system of medicines has certainty with safer medications to treat children. Children with CP have multiple symptoms for which no curative treatment exists. Manipulative and body based methods such as Thokkanam, Podithimirthal to improve the quality of life of CP children. The trial drug Kurunthotti kudineer along with kollu podi thimirthal and Vasavu ennai massage was treated to the children. Kurunthotti Kudineer’s primary use is to enhance cognitive function. Researchhas been focused on the mechanism behind these properties