Ayurvedic approach in the management of spinocerebellar ataxia-2.

Spinocerebellar ataxia -2 is a progressive, degenerative genetic disease caused by an expanded (CAG) trinucleotide repetition on the chromosome 12 resulting in production of an abnormal protein called ataxin-2. There is no known effective management or cure in biomedicine for this genetic disease. In the present study a case of SCA2 that was treated with Ayurvedic intervention is reported. Ayurvedic treatments in this case were directed towards alleviating symptoms and to reduce severe disability due to progressive nature of disease. A 42 year old male patient was diagnosed for Vāta vyādhi (group of various neurological disorders) and was- treated with Śālisastika pinda svedana (sudation with bolus of medicated cooked rice) for 30 days-, Śirobasti (sudation of head with the help of a cap on head) with Aśvagandhā taila for 45 days and Balādi ksīra basti (enema with medicated milk) with Aśvagandhā taila anuvāsana (enema with oil) for 30 days in Karma basti krama (30 days regime of purification and oleation enema) along with a combination of Ayurvedic oral drugs which consisted of Brahadvātacintāmanirasa - 125 mg, Vasantāmaltī rasa- 125 mg, Daśamūla kvātha- 40 ml, Aśvagandhā cūrṇa (powder of Withania somnifera DUNAL)- 3g, Amrtā cūrṇa (powder of Tinospora cordifolia Willd.)- 500 mg, Muktāśukti pisti - 500 mg, Yogarāja Guggulu - 500 mg twice a day for 2 months. Patient's condition was assessed on the Scale for Assessment and Rating of Ataxia (SARA). Before treatment, mean SARA score was 35. This reduced to 15 after treatment. Good relief in dysarthria, fasciculation, heaviness in eye, blurred vision, axial tremor; constipation and quality of life were observed in this case.

INTRODUCTION

Spinocerebellar ataxia -2 is a genetic disease caused by the mutation of SCA2. This mutation causes repetitions of the trinucleotide (CAG) 8CAA (CAG) 4CAA (CAG) 8 within the ATXN2 gene exon 1 located on chromosome 12q24.1. This results in the production of an abnormal protein called ataxin-2.[1] The worldwide prevalence of SCAs is estimated at about 6 cases per 100,000 people.[2] Families- suffering from SCA2 have been found in Australia, Germany, Italy, India, Martinique, Tunisia, Mexico, Poland and especially in Cuba. SCA2 was first recognized in India in 1971 by Wadia and Swami, who were working on the early slowing of saccade movements, associated to the cerebellar syndrome.[3] The variant SCA2 is the second most prevalent subtype worldwide, followed by SCA3 among the almost 30 SCAs.[4] The clinical picture of SCA2 includes a cerebellar syndrome in all patients, characterized by ataxic gait, cerebellar dysarthria, dysmetria and dysdiadochokinesia, abnormal tandem stance, limited voluntary ocular movements, slow saccadic eye movements, loss of vibration sense, areflexia or hyporeflexia after initial hyperreflexia and abnormal swallowing.[5] Autonomic abnormalities (hypohidrosis, urinary dysfunction, constipation, and sexual dysfunction) are present in 78% of the cases and are accentuated in the late stages of the disease, together with dysphasia, ophthalmoplegia and distal amyotrophy.[6] Sleep disturbances are frequent complaints of SCA2 patients and their relatives. The most prominent sleep disorders are restless legs syndrome, insomnia, muscle cramps, and reduced dream recalls. The cognitive dysfunctions, which include frontal executive impairment, verbal short-term memory deficits as well as reduction of attention and concentration, are other clinical manifestations of SCA2. The mean age of onset is 33 years which varies from 3 to 79 years. Symptoms usually begin in the third or fourth decade of life. Usually, the first symptom of the disease is the gait ataxia, followed by cerebellar dysarthria. Till date, there is only one reported Ayurvedic study in PubMed indexed journals which reports satisfactory improvement in cerebellar ataxia.[7] Substantial recovery was reported by the authors of the said study through Ayurvedic management. This is important because no treatment is available in biomedicine for this genetic disease.

CASE REPORT

A 42 year old male came to O.P.D. of National Institute of Ayurveda Jaipur on April 16, 2014 with complaints of difficulty and unsteadiness in walking and impaired speech. Patient was unable to stand from sitting posture and was unable to walk without support. During normal conversation his speech was not understandable. Patient also suffered from insomnia, urinary dysfunction, sexual dysfunction and constipation. Blurred vision and heaviness in eye were also present. The disease was progressive in nature that first affected lower limbs and then his upper limbs. Patient suffered from the disease since last 16 years. Patient had consulted neurology department of AIIMS New Delhi and Sir Ganga Ram Hospital New Delhi 14 years before coming to us. The diagnosis using genetic mapping indicated SCA-2, i.e. Autosomal Dominant Cerebellar Ataxias (ADCA-1). Patient had strong family history with anticipation. Due to unavailability of satisfactory treatment and failing to get any response from allopathic treatment, the patient decided to take Ayurvedic treatment. Patient was diagnosed for Vāta vyādhi (group of various neurological disorders) and was admitted in male Pancakarma ward of National Institute of Ayurveda, Jaipur India for administration of Pancakarma procedures.

Clinical findings

On physical examination patient was found to be anxious with reduced sleep, had moderate appetite, visamāgni (unstable digestive functions), bowel constipated, burning micturition with reduced frequency, tongue clean, voice clear, skin rough and lean body built. His intelligence was normal and had a vātapitta prakrti with madhyama sāra (medium purity of body tissue), madhyama samhanana (medium body built), sama pramāna (equal body proportions), avara sātmya (least homologation), madhayam sattva (medium mental strength), avara vyāyāmśakti (least physical endurance), madhyama āhāraśakti and jaraanśakti (medium food intake and digestive power). Majjāvāha srotodusti (pathology in bone marrow) was more prominent. On eye examination, ocular apraxia was found, saccades and pursuits were affected. On motor examination, facial, truncal and upper limbs fasciculation was found. The bulk, tone and power of muscles were normal. Stretch reflexes were normal and plantar flexor, sensory examination was normal. Cerebellar signs (such as intention tremor, past pointing in the finger nose test, dysdiadochokinesis and truncal ataxia) were positive. Skin, cardio respiratory, musculoskeletal and genitourinary system examinations were normal.

Timeline

A detail of the case study and follow up is given in Table 1.

Table 1

Timeline

Diagnostic assessment

Patient was a known case of SCA 2. It was previously confirmed by genetically mapping. In an M.R.I. scan of brain, cerebellar atrophy was revealed. Previous hematological investigation and electrophysiology were normal. Patient suffered from gadgadatva (impaired speech) kampa (tremor), kālayakhañjatā (Limping with tremor at the starting of movement), anidrā (insomnia), mūtranigraha (urinary dysfunction), purīsa-apravrtti (constipation), paribhram (vertigo and imbalance), sphurana (fasciculation) etc. These diseases are counted in nānātamaj vāta vyādhis (disease only due to vāta dosa).[8] Hence this disease is a group of nānātmaja vāta vyādhis and vāta vyādhi was concluded to be the Ayurvedic diagnosis. The disease was considered as asādhya (incurable).

Intervention

Considering the asādhya (incurable) nature of disease, Ayurvedic management was directed to ameliorate the various symptoms and complication of the disease. Castor oil in doses of 30 ml on two consecutive nights was given to treat constipation. From the next day, the patient was advised a combination of oral Ayurvedic drugs that included Brhadvātacintāmani rasa – 125 mg, Vasantamāltī rasa- 125 mg, Daśamūla kvātha 40 ml, Aśvagandhā cūrṇa (Withania somnifera)-3 g, Amrtā cūrṇa (Tinospora cordifolia) – 500 mg, Muktāśukti pisti- 500 mg and Yogarāja Guggulu - 500 mg twice a day for 2 months [Table 2] and Ayurvedic Pancakarma interventions were given in Table 3. Patient was treated with Śālisastika pinda svedana (sudation with bolus of medicated cooked rice) for 30 days, Śirobasti (sudation of head with help of a cap on head) with Aśvagandhā taila for 45 days and Balādi ksīra basti (enema with medicated milk) with Aśvagandhā taila - anuvāsana (enema with oil) for 30 days in Karma basti krama (30 days regime of purification and oleation enema).

Table 2

Ayurvedic treatment given to a case of spinocerebellar ataxia-2

Table 3

Panchakarma procedures adopted in a case of spinocerebellar ataxia-2

Follow-up and outcomes

On June 18, 2014 the patient's condition was assessed on the Scale for Assessement and Rating of Ataxia (SARA).[9] Before treatment, mean SARA score was 35. This reduced to 15 after treatment. After 2 months of treatment, the patient was able to stand from the sitting position. He was able to walk without support [Video 1]. He was able to turn during walking [Video 2]. His speech was improved and it was easily understandable [Video 3]. Autonomic dysfunctions improved. Heaviness in the eye, insomnia and constipation was relieved. All investigations (CBC, ESR, Hb%, ASLO, CRP, Blood sugar, Lipid profile, LFT, Urine-routine and microscopic) were normal. Patient and his relatives were satisfied with the clinical outcomes. At time of discharge, patient was advised to repeat the Pancakarma therapies at two month intervals for longer durations to gain optimum relief.

DISCUSSION

The Autosomal Dominant Cerebellar Ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of neurodegenerative disorders caused by degeneration of cerebellum and its afferent and efferent connections. The degenerative process may additionally involve the Ponto - medullar systems, basal ganglia, cerebral cortex, pyramidal tracts, and peripheral nerves.[10] This is a degenerative disorder in which central nervous system -peripheral nerves, and muscles are affected. The patient was diagnosed for Vāta vyādhis as dhātuksaya (~depletion of nutrition and tissues) is the main causative factor and pathology in the disease. The general line of treatment for Nānātmaja vāta vyādhis was taken into consideration for the case. Patient was treated with Pancakarma procedures along with a combination of drugs as discussed above with satisfactory clinical outcome.

Considering the Dhātukshaya, Santarpana (~treatment of nutritional deficiency) in the form of Balādi ksira basti with Aśvagandhā taila anuvāsana, Śālisastika pinda svedana and Śirobasti with Aśvagandhā taila was given. This resulted in significant improvement in this patient. Mahāpanñcatiktaghrta and soup of goat femur bone marrow are used as contents of the Balādi ksīra basti [Table 3]. In Ayurveda, brain is considered to be form of majjādhara kalā.[11] Unsteadiness and blurred vision are described in majjā-pradosaja vikāras (diseases produced in vitiated majjā dhātu).[12] In majjāgata diseases tiktādi and madhura drugs are indicated.[13] Slight modification was done for the basti, in that majjā (long bone marrow) obtained from goat femur bone marrow was used.[14] Tiktadi drugs in the form of Mahāpanñcatiktaghrta[15] and Aśvagandhā taila were used.[16] Local abhyaṇga (oleation/massage) and svedana (sudation) on lumbosacral region, inguinal region and lower abdomen were administered before each basti.

Balādi ksīra basti used in this case is a modification of Yāpana basti (enema for sustaining health).[17] In this case, Balādi ksīra basti was given with Aśvagandhā taila anuvasāna for 30 days in Karma basti krama. Relevant biochemical finding in SCA2 patient is the significant reduction of erythropoietin levels in the CSF.[18] Erythropoietin is a cytokinin for erythrocyte precursors in the bone marrow. Thus, application of long bone marrow through the basti route may be helpful in the treatment of SCA2. Śirobasti is indicated in Śirahkampa (axial tremor) and heaviness of the head in Ayurveda.[19] In this case Śirobasti was done with Aśvagandhā oil. This oil has vātaśāmaka and Brhmana (anabolic) properties. Śirobasti is indicated for five to seven days or more in śirorogas (diseases of the head). Primary lesion of this disease was in the brain. Śirobasti was given for 45 days in this case due to chronicity of more than 16 years of this disease in the patient case.

Śālistika pinda svedana has the nourishing effect on muscles and peripheral nerves. It is effective in fasciculation, peripheral neuropathy and dysponea due to muscle atrophy of respiratory muscles. The main cause of death in this disease is bronchopneumonia (63%), followed by bronchial aspiration and cardiovascular incidents. These disorders may be remitted with application of Śālistika pinda svedana. Significant reduction of zinc, iron and copper levels in the CSF and serum of SCA2 patients is also a major finding.[20] Zinc has the important role in the control of synapses in the cerebellum. The reduction of zinc levels could be associated with slowing of nerve conduction, cognitive dysfunction, and immune-depression at final stages of the disease and could accentuate the dysfunction of cerebellar circuits. Oral drugs used in this case were Brahadvātacintāmanirasa – 125 mg, Vasantāmaltī rasa- 125 mg, Daśamūla kvātha- 40 ml, Aśvagandhā cūrṇa (Withania somnifera DUNAL)- 3g, Amrtā cūrṇa (Tinospora cordifolia Willd.)- 500mg, Muktāśukti pisti – 500 mg, Yogarāja Guggulu – 500 mg that were given twice a day for 2 months, also have zinc and iron in mineral form as ingredients that may be useful in this disease. Brhadvātacintāmaṇi rasa is indicated in all type of Vātaja (disease due to vāta dosas) and respiratory diseases.[21] Vasantmālatī rasa helps in improvement of metabolic activities at tissue level (agni pradipti) and also alleviates depleted condition of body.[22] Daśamūla kvātha is useful in all types of vātaja and respiratory disorders and has tridoṣaghna (alleviating deranged dosas of the body) property.[23] Aśvagandhā[24] and Amṇtā have balya (anabolic) and rasāyana (immunomodulator) properties.[25] Muktāśukti piṣṭi is helpful in G.I.T. disorders such as hyperacidity and in udara roga (splenic and hepatic diseases).[26] Yogarāja Guggulu is useful in all types of Vātaja and neurodegenerative disorders.[27] SCA-2 patients with larger CAG repeats have earlier age at onset, more saccadic slowing, axial tremor, mental deficit, pyramidal-dystonic-choreic signs and in general a faster progression to death. Clinical features develop progressively with an increase in cerebellar syndrome, saccade slowing, and other features that confine the patients first to a wheelchair and subsequently to a bed, where they die approximately 15–20 years after the initial symptoms.[28] First sign in this patient was observed at the age of 27 years.

Good relief in dysarthria, fasciculation, heaviness in eye, blurred vision; axial tremor and constipation were observed in this case. Gradual improvement was noticed in every two weeks in this case but assessments for scoring were done only at the beginning and at the end of treatment. SARA score in this patient was 35 before treatment which reduced to 15 after treatment. At the end of treatment, the patient was advised to repeat Pancakarma procedures after 2 months as this much time is needed for administration of further Basti procedures. He was readmitted on August 25, 2014 and same management was adopted. The patient was admitted again from Sept 1, 2015 to Oct 20, 2015 for Pancakarma procedures - At this time SARA score was 10. Now the patient is under continuous follow up for observation and treatment and his condition is stable and has hopes of complete recovery from this disease. We found no worsening of any symptoms and signs till date. This is an important finding considering the prognosis and non availability of treatment in bio-medicine. This case study shows that patients suffering with SCA -2 can be treated with Ayurvedic management with satisfactory outcomes. This combined Ayurvedic treatment with oral vāta pittahara (suppressors and eliminators of deranged vāta and pitta dosas) drugs along with Śālistika pinda svedana, Śirobasti and Balādi ksira basti may be considered for further treatment and research on SCA-2.

CONCLUSION

SCA - 2 can be managed with satisfactory outcome with Ayurvedic medicine and Pancakarma procedures. This case study shows that the SCA – 2 patients may be satisfactory treated with Ayurvedic management. These findings may prove helpful for conducting further treatment and research work for SCA -2 2 and other similar conditions.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Patient's perspective: Relatives of the patient were satisfied with the provided treatment [Video 4].

Financial support and sponsorship

National Institute of Ayurveda, Jaipur.

Conflicts of interest

There are no conflicts of interest.