An open labelled rct study to assess the combined effect of nasapana with mashabaladikwatha , prachandabairavarasa and paravat kalpa over mashabaladitaila pratimarshanasya, ardhangavatarirasa, paravat kalpa in ischemic stroke (margaavarana janya pakshaghata)

NEED FOR THE STUDY

Stroke is a state of decreased oxygen supply to brain cells leading to the tissue death and defined as an acute focal neurological deficit resulting from cerebrovascular disease and lasting more than 24hrs1. Ischemic stroke is caused by thrombotic or embolic occlusion of a cerebral artery and is more common than hemorrhagic stroke2.  Stroke is the second commonest cause of death in India. About 1,85,000 strokes occur every year in India with nearly one stroke every 40 seconds and one stroke death every 4 minutes In India, studies estimate that incidence of stroke population varies from 116 to 163 per 100,000 population, it is the 4th leading cause of death and 5th Leading cause of Disability Adjusted Life years (DALY) - 2016.3

Pakshaghata4 being one among the 80 nanatmaja vatavyadhis, is caused either by Margavarana or Dhatukshaya or Margavarana leading to Dhatukshaya. The clinical symptoms: Karma kshaya, Balahani over one Paksha looks similar to the hemiplegia / hemiparesis in contemporary medicine.

In Pakshaghata, Margavarana, Sira Snayu Shosha, Srothorodha, Sthambha, Sankocha seems to be present in every subjects.  The ischemia leading to tissue death inside the brain has to be considered Margavarana leading to Dhatukshaya5.The administration of anti coagulants, cerebral  activators etc., eventhough being commonly prescribed, the results are not upto the mark. The  researches upon activating the brain cells, reducing muscle rigidity and  improving motor  functions via various medical systems are going on. So research is needed.

Madhoodaka pana6 is medahara, Avaranaghna, Ruksha, Deepana, Lekhana pachana and vatanulomana. Sneha virechana is classical chikitsa sutra 7 with Payasa Eranda taila is effective in Neurotoxin deposition, neuroendocrine metabolism, anti inflammatory, analgesic, anti spasticity.

Nasapanaand nasya are transnasal administrations targetted on vyadhiadhishtana. The Mashabaladi Kashaya9 is a special Brumhana yoga  used for nasapana. Prachanda Bhairava rasa10, a Kajjali and

Tamra Bhasma kalpa,where in Tamra Bhasma is  Teekshna Lekhana Rasayana used generally in vascular blocks. The yoga is indicated for Kampa, Ardhanga vata, daha ,Santapa Ruja etc., Paravata kalpa1 Prayoga is Grathitha Rakthahara, contains iron, saponins and electrolytes, antiplateletaggregating novel approach in thromboembolic stroke  which implies its anticoagulant activity. Research question is weather ayurvedic blood thinners and anti-inflammatory  approach

has any role in stroke in one arm and simple opd level rogayoga  easy approach with  ardhangavatari rasa, paravatakalpa and mashabaladitaila pratimarshanasya is effective is thought. Also two kajjali kalpas with same ingredients but different names will also be clinically studied to find their clinical effect. So set of classical  interventions or simple opd level shamana chikitsa has  combined effect in activating the brain cells, reducing muscle rigidity and improving motor functions is alternately hypothesized to bring a breakthrough in the field.

Hence the present study entitled “AN OPEN LABELLED RCT STUDY TO ASSESS THE COMBINED EFFECT OF NASAPANA WITH MASHABALADIKWATHA, PRACHANDABAIRAVARASA AND PARAVATKALPA OVER MASHABALADITAILA PRATIMARSHANASYA, ARDHANGAVATARIRASA, PARAVATKALPA IN ISCHEMIC STROKE (MARGA AVARANA JANYA PAKSHAGHATA)” is taken.

HYPOTHESIS:

•        H0- NasaPana with Mashabaladikwatha, Prachandabairavarasa & Paravat kalpa and Mashabaladi Pratimarsha nasya and Ardhangavatarirasa, Paravatkalpa in ischemic stroke has no effect.

•        H1-Nasapana with Mashabaladikwatha, Prachandabairavarasa & Paravat kalpa and Mashabaladi Pratimarsha nasya and Ardhangavatarirasa , Paravatkalpa  in ischemic stroke has effect.

OBJECTIVES OF THE STUDY:

1.   To assess the combined  effect of madhoodaka pana, Sadyo virechana  with payasa eranda taila, abhyanga with lashuna taila and mashabaladi kwatha nasapana, prachandabhairav rasa and Paravatakalpa in ischemic stroke.

2.   To assess the combined  effect of madhoodaka pana, Sadyo virechana  with payasa eranda taila, abhyanga with lashuna taila  and mashabaladi pratimarsha nasya and ardhangavatarirasa , paravat kalpa  in ischemic stroke .

3.  To compare the efficacy of madhoodaka pana, Sadyo virechana  with payasa eranda taila, abhyanga with lashuna taila and mashabaladi kwatha nasapana, prachandabhairav rasa and Paravata kalpa over madhoodaka pana, Sadyo virechana  with payasa eranda taila, abhyanga with lashuna taila  and mashabaladi pratimarsha nasya and ardhangavatarirasa , paravatkalpa  in ischemic stroke .

 DESIGN OF STUDY***:***

✓    Study type – Interventional, randomized, controlled.

✓    Estimated enrolment – 40 (20 in each groups)

✓    Allocation – Randomised, two arm

✓    Masking – open labelled

✓    Primary purpose – Treatment

✓    Duration of study - 34days

✓    Followup- 14 days

ASSESSMENT CRITERIA:

Subjective parameters:

✓  Chesta nivrutthi (Motor weakness)

✓ Ruja in affected part of the body (Pain in affected part)

✓  Vaksthambha (Slurred speech)

✓  Stambha (Stiffness)

✓  Supti (Sensory loss)

✓  Mukhavakrata (Facial deviation)

GRADING FOR SUBJECTIVE PARAMETERS:

SUBJECTIVE PARAMETERS:

GRADINGS

  |RUJA

Grade 4 (CD)

Very severe intolerable,Persistent pain

treatment

|Grade 3 (CD)

Severe intolerable pain unable to carry work without treatment

|Grade 2 (CD)

Moderate tolerable pain able to work with difliculy

Grade

|Grade 1(CD)

Minimal pain able to work easily

|Grade 0 (CS)

Pain is absent patient is.clinically stable

|STAMBHA

Grade 4 (CD)

Very severe stiflness present with treatment

|Grade 3 (CD)

Severe stillness present without treatment

|Grade 2 (CD)

Moderate stiffness

|Grade 1(CD)

Minimal stiflness

|Grade 0 (CS)

No stifiness clinically stable

|KARMA HANI

Grade 4 (CD)

Unable to work at all not relieved by treatment

|Grade 3 (CD)

Relieved by treatment work with difliculty

|Grade 2 (CD)

Relieved by exercise and food

|Grade 1(CD)

Able to work easily

|Grade 0 (CS)

No loss of movements at all

|MAMSA SHOSHA

Grade 4 (CD)

Very severe visible bulk Fixed

|Grade 3 (CD)

Markedly decreased muscle bulk

|Grade 2 (CD)

Moderate decrease in muscle bulk

|Grade 1(CD)

Mild decrease in muscle bulk

|Grade 0 (CS)

Normal muscle bulk

|MUSCLE POWER

Grade 4 (CD)

No visible or palpable contraction

|Grade 3 (CD)

Flicker or.trace contraction

|Grade 2 (CD)

Active movement with gravity eliminated

|Grade 1(CD)

Active movement against gravity and resistance

|Grade 0 (CS)

Normal power

|MUKHA VAKRATA

Grade 4 (CD)

Permanent deviation of mouth

|Grade 3 (CD)

Alternate deviation of mouth

|Grade 2 (CD)

Moderate deviation of mouth

|Grade 1(CD)

Mild deviation of mouth

|Grade 0 (CS)

No deviation

|VAK KRICHRATA

Grade 4 (CD)

Always no speech at all

|Grade 3 (CD)

Often speaks sometime. unclear

|Grade 2 (CD)

Slurred speech with difficulty

|Grade 1(CD)

Mild audible understandable speech

|Grade 0 (CS)

No difficulty in speech

    

National Institutes of Health Stroke Scale (NIHSS)13

   |Instructions

Scale Definition

   |1a. LOC

0 = Alert keenly responsive

 1 = Not Alert but arousable by minor stimulation to obey, answer, respond

 2 = Not Alert; requires repeat stimulation, obtunded, requires strong stimuli

 3 = Reflex motor or autonomic effects response, totally unresponsive, flaccid

|1b. LOC Questions. Ask the patient the month & age

0 = Answers both

questions correctly

1 =   Answers one question correctly

2 = Answers neither questions correctly

|1c. LOC Commands. Ask to open & close eyes, then grip & release with non-paretic hand.

0 = Performs both tasks correctly

1 = Performs one task correctly

2 = Performs neither task correctly

|2**. Best Gaze**. Asked to follow with eyes thru horizontal plane (or oculocephalic maneuver).

0 = Normal

 1 = Partial Gaze Palsy; gaze is abnormal in 1 or both eyes, but forced deviation or total gaze paresis is not present.

 2 = Forced deviation; total gaze paresis not overcome by oculocephalic man.

|3. Visual fields (quadrants) tested with finger counting or visual threat.(done by confrontation)

0 = No visual loss

 1 = Partial hemianopia

 2 = Complete hemianopia

 3 = Bilateral hemianopia (including cortical blindness).

|4. Facial Palsy. Asked to show teeth & raise eyebrows

0 = Normal symmetrical movement

 1 = Minor paralysis (flattened nasolabial fold, asymmetry on smiling) 2 = Partial paralysis (total or near total paralysis of lower face)

 3 = Complete paralysis of one or both sides (no upper/lower face mvmt).

|5. Motor Arm. Asked to extend arms (palm down) 90º (if sitting) or 45º (if supine) & hold for 10 seconds. Begin with non-paretic limb.

0 = No drift; limb holds 90º(or 45º) for full 10 seconds

 1 = Drift, limb holds 90º(or 45º) but drifts down before full 10 seconds but does not hit bed or other support

 2 = Some effort against gravity, limb cannot get to or maintain (if cued 90ºor 45º) drifts down to bed, but has some effort against gravity.

 3 = No effort against gravity, limb falls

 4 = No movement

*UN = Amputation, joint fusion: Explain

|6. Motor Leg. While supine, asked to hold leg at 30º for 5 seconds.

0 = No drift; leg holds 30º for full 5 seconds

 1 = Drift, leg falls but does not hit bed

 2 = Some effort against gravity, falls to bed

 w/in 5 sec

 3 = No effort against gravity; leg falls to bed immediately

 4 = No movement

*UN = Amputation, joint fusion: Explain

          |7.Limb Ataxia. Finger – nose & heel – shin test on both

Sides

0 = Absent

1 = Present in one limb

 2 = Present in two limbs

 *UN = Amputation, joint fusion: Explain

|8. Sensory. Sensation or grimace to pin prick or withdrawal from noxious stimuli to limbs in obtunded or aphasic patient.

0 = Normal, no sensory loss

 1 = Mild/moderate sensory loss; may be dulled/”Not as sharp”

 2 = Severe/total sensory loss; not aware of face/arm/leg being touched.

|9.Best Language. Describe what is happening in picture, name items of figures, read list of sentences on attached figures.

0 = No aphasia, normal

 1 = Mild / moderate aphasia; some loss of fluency / comprehension, without limitation of expression of ideas. (can identify what is happening in picture)

 2 = Severe aphasia; (cannot identify pictures)

 3 = Mute; global aphasia; no usable speech; or auditory comprehension

|10.Dysarthria. Read or repeat words from list.

0 = Normal articulation

 1 = Mild / Moderate; slurs some words; understood w/some difficulty.

 2 = Severe, so slurred as to be unintelligible; mute/anarthric

*UN = Intubated or other physical barrier. Explain

|11.Extinction & Inattention.

Look at visual (from #3) and double simultaneous tactile. Do both arms & legs.

0 = No abnormality

 1 = Visual, tactile, auditory, spatial or personal inattention or extinction to bilateral stimulation in one sensory modalities.

 2 = Profound hemi-inattention or inattention to more than one modality; does not recognize own hand; orients to only one side of space.

|*UN = untestable

 TOTAL SCORE

  |

OBJECTIVE PARAMETERS:

•   Strength, bulk, tone of the muscle

•   Deep tendon reflexes.

•   superficial tendon reflexes

•   PTINR

•   Sr lithium

•   Homocysteine

INVESTIGATIONS

·       Hb, TC. DC. ESR, RBS, PTINR, APTT, LIPID PROFILE lft, lithium

·       CHEST X-RAY, NECK VESSEL DOPPLER, ECG, CT, MRI brain and other investigations if needed.

DATA WILL BE COLLECTED ON

Subjective parameters will be collected on

0TH DAY - Before treatment

11TH DAY- During treatment

35TH DAY- After treatment

After 15 days of follow up

Objective parameters will be collected on

Before treatment and after treatment

OVERALL ASSESSMENT:

•        Marked relief-above 75% improvement

•        Moderate relief-51%-75% improvement

•        Mild relief -25% -50% improvement

•        No relief - 0% improvement