MESODIENCEPHALON MODULATION V.A.Karev MD,PhD, A.V.Melerzanov MD,PhD

ACTG-adrenocorticotropic hormone BA–bronchial asthma

BP–blood pressure CCT-craniocerebral trauma

CNS-central nervous system CF-circulatory failure

CFS – chronic fatigue syndrome COPD – chronic obstructive pulmonary disease

DM-diabetes mellitus ED-erectile dysfunction

FEV-forced expiratory volume GYN-gynecology

HT- hypertension ICP-infantile cerebral palsy IHD-ischemic heart disease IS-ischemic stroke LV-left ventricle MDM –mesodiencephalon modulation MI-myocardial infarction PEFR- peak expiratory flow rate

RV-right ventricle STH-somatotrophic hormone

Neuro-endocrine system and adaptation.

Our days it is been set that “life quality” means resistance to damaging factors, capacity for work, physical and psychological endurance, psychological status are being determined by functioning level of “adaptation system”. Condition of a human organism in the extreme conditions (high psychological and physical burden, toxic and environmental impacts, acute and recurrence of chronic diseases) depends on quality of “adaptation response”. With sufficient reserves of the adaptation system, adaptive potential is high and it allows human organism to tolerate extensive overloads. In case of insufficient functioning of the adaptation system (worst case — dysadaptation syndrome) tolerance even for comparatively low loads is inadequately low.

Stress-reaction is a necessary starting component for immediate adaptation; simultaneously damaging components of stress may have a negative impact at functions of organs and systems including the adaptation system.

Quality of forming of immediate and long-term adaptation in the first turn depends on adequate functioning of neuro endocrine system with centers located in mesencephalon. Part of this system is opioid system producing over 40 neuro hormones (opioid peptides) mainly for protection from stress, pain relief and coordination of functional systems at the level of the whole organism. Second system that defines quality of the adaptation response is hypothalamic hypophysial system with main function of tuning of endocrine glands functions and tissues metabolism according to changing internal and external conditions.

Last years it has been detected that CNS is involved into regulation of hormones production by endocrine glands, hormones in their turn have the influence at CNS functioning by modification of its activity. Neuro regulation of endocrine functions is performed through hypothalamic and hypophysial hormones and by the autonomic nervous system monoamines. Peptide hormones (vasoactive intestinal peptide, cholecystokinine, gastrin etc) are secreted in different parts of CNS and in endocrine cells of gastrointestinal tract as well.

Opioid and hypothalamic — hypophysial systems closely linked functionally to each other and located close by in mesencephalon. Functioning of the neuro endocrine system is synchronized with immune system, so term “neuro endocrine immune complex” started been used lately.

2 MDM

Clinical use of transcranial electrotherapy has started in 1902 and since then was developing mainly for sedation and anesthesia. MDM utilizing previous achievements based on modifying of the electrical impulse for normalization of work of centers regulating adaptation system and located in opioid and hypothalamic — hypophysial system.

2.1 How MDM works.

Due to a chronic stress and bad environment typical for modern civilization 80% of population has their neuro-endocrine systems acting at 70-90% of the desired level. 95% of population after 60 y.o. have their systems act at 50-70% level that partially defines aging process and development of chronic diseases. Meanwhile human brain has reserves that can normalize conditions of neuro endocrine centers for prolonged periods without any harm.

Regular stimulation of neuro endocrine systems provides move to upper level of adaptation and antistress activity that increases as release of neuro hormones from depot so their synthesis. That is the pathway MDM works.

Fig.1 shows dynamics of biochemical parameters reflecting intensity of stress reaction and adaptation response at some disorders (acute MI, burns, stomach and duodenum ulcers with bleeding). General biological defense reaction from stress factors forming immediate and long-term adaptation is being registered.

As shown at fig.1 starting with first hours of damaging impacts (diseases, physical and emotional stress) concentration of stress markers (free radicals, cortisole) and of opioid peptides (opioid peptides) in peripheral blood increases. Later (2-3-d days) with background of increasing concentration of dien conjugates and cortisole dramatic decline of B-endorphins concentration is observed, that shows depletion of endogenous antistress and anesthetic systems with simultaneous suppression. Rebuilding of opioid and immune systems progresses slowly reaching initial numbers only by day 10. Simultaneously concentrations of anabolic hormones — STH and insulin increase that reflects the process of forming of immediate and long-term adaptation. If concentration of STH and insulin remains low in first 3 days without growth it’s a sign of “dysadaptation syndrome” that comes to a fatal outcome in some cases of urgent conditions.

Fig 1 Generalized dynamics of biochemical markers of stress and adaptation in patients with urgent conditions: 1 diene conjugates (free radicals), 2 cortisole, 3 STH, 4 insulin, 5 integral indicator of immune system condition, 6 B-endorphin

Quality of the “adaptation response” depends on:

1Background (initial) condition of the adaptation system

2 Intensity of overload

3 Intensity of damaging stress components causes appearance of vicious circles at systemic, organic and tissues levels. Most important are processes with negative impacts at neuro-endocrine system.

MDM therapy start

Fig.2Generalized dynamics of biochemical markers of stress and adaptation in patients with urgent conditions with MDM-therapy background: 1 diene conjugates (free radicals), 2 cortisole, 3STH, 4insulin, 5 integral indicator of immune system condition, 6 B-endorphin

With daily MDM-therapy (10-15 days starting from the first day of disease) changes at dynamics of stress-reaction and adaptation system is clearly shown (fig.2). After the first treatment blood concentration of free radicals and cortisole drops that shows antioxydant and antistress action. Also concentration of anabolic hormones (STG and insulin) grows which is a sign of immediate adaptation. At a third day of the MDM-therapy faster rebuilding of opioid and immune systems with a statistically proven difference at concentration of opioid peptides between two groups were observed.

Change of the adaptation system condition is accompanied by change of the whole organism functioning at organs and tissues levels. Activities of organs get synchronized together with changes of biochemical process particularly in defected organs with hypoxic conditions that allows adequate energy supply by despite of the oxygen deficiency (antihypoxant effect).

2.2. MDM devices

First generation of MDM device was developed in 1986 and introduced in 1990, next generation was created in 1992. In 2001 new device Medapton-4 was certified for medical use (shown at fig.3). Medapton provides maximal purity of the electrical impulse with interchanging constant and intermediate current with circularly changing frequency between 70 and 90 Hz with 6 waves configurations (fig.4) and duration of each impulse for 4 ms.

 

Fig. 3

Battery operated portable device is very suitable for the individual use for professional sportsmen, emergency medicine, rehab patients and people practicing healthy lifestyle.

 

Fig. 4 Wave forms of electrical impulses supplied to electrodes

MDM-therapy based on stimulation by low strength electrical impulses of programmed waves types of centers of opioid and hypothalamic — hypophysary system located in mesencephalon and diencephalon with minimal reaction of other cerebral structures.

3. Clinical use of MDM

Data on clinical efficacy of MDM in different disorders from last 20 years are shown at table 1

 

Disorder

Clinical effect

1

IHD: angina pectoris

decreasing frequency of AP attacs, increasing of physical endurance due to increasing of collateral coronary blood flow.

2

IHD: MI

Reduction of number and intensity of complication in all periods, faster reparation process with less % of disabilities and lowering of quantity of medicines taken

3

HT

Relief of hypertensic crisis and complications, stabilization of BP with lowering quantity of medicines taken

4

CF

Condition severity improving by increasing of cardiac propulsive ability, of pulmonary membranes permeability, of peripheral blood flow and tissue metabolism

5

BA

Combined therapy of asthmatic status, improving of external breathing and gaz exchange, prevention of relapse up to reduction of hormonal therapy

6

Bronchitis

Faster recovery, less complications and prevention of relapse

7

Pneumonia

Faster recovery, less complications particularly in immunodeficiency

8

Stomach and duodenum ulcer

Faster ulcer healing, better hemodynamic in case of bleeding, pain relief and prevention of relapse, maybe used as monotherapy

9

Gastritis

Acidity normalization, faster recovery and prevention of aggravation

10

Cholecystopancreatitis

Pain relief, reduction of inflammation, prevention of aggravation

11

DM

Reduction of complications, prevention of developing of polyneuritis, diabetic foot, retinopathy and reduction of quantity of medicine taken.

12

Arthritis

Pan relief, anti-inflammatory action, prevention of aggravation

13

Surgical diseases

Before and after surgery care. Reduction of stress-reaction, prevention of complications, faster healing and recovery of operated organs

14

. Burns and frostbites

Antistress effect, pain relief, faster reparation, prevention of complications and lowering of quantity of medicines taken

15

Injuries

Lowering of frequency of complications and disabilities, pain relief, faster reparation

16

GYN diseases

Faster recovery, pain relief, prevention of aggravation

17

Pyelonephritis

Shorter inflammation period, prevention of aggravation

18

Radiculitis, neuritis

Pain and inflammatory relief, monotherapy

19

Osteochondrosis

Pain relief, prevention of aggravation

20

Neurocirculatory dystonia

BP stabilization, reduction of vegetative nervous system disorder, improving of psychological status

21

Neurodermatitis, eczema

Reduction of itching and skin rush, remission, monotherapy

22

Psoriasis

Reduction of itching and skin rush, remission, monotherapy

23

Tonsilitis

Pain and inflammatory relief, faster recovery

24

Common flu

3 days recovery, complication prevention, monotherapy

25

Antritis

Faster recovery, prevention of aggravation

26

Periodontitis

Pain relief, inflammation reduction 4 days, monotherapy

27

Neuroses

Psychological status normalization, faster recovery, potential monotherapy

28

ED

Better psychological status and erection

29

Speech pathology

Higher efficiency (20-25%) of combined therapy

30

Pediatry

Antistress effect, normalization of immune, other systems and reparation.

There is only one absolute contraindication detected – presence of metal particles in the brain, also if MDM is prescribe for a patient with epilepsy or acute period of schizophrenia, treatment has to be performed under observation of the neurologist or psychiatrist respectively.

Side effects:

Headaches in 3-5% of cases after first 1-3 treatments, disappears by 4-th treatment, in cases of persistent headaches (very rare case) type of waves should be changed and if headache persists cease the treatment. Usually these headaches appear in patients with breached venous drainage due to organic reasons.

Redness of the electrode placement site on a forehead in 8-10% – disappears with use a moisturizer after each treatment

Major effects:

1. Antistress in urgent and chronic cases, emergency medicine, preparation for surgery and rehab after injuries, surgery and acute ischemic incidents, chronic stress, asthenia and depression related to chronic long lasting diseases

2. Lowering of reparation time for patients with acute MI, fractures, burns and stomach ulcer with bleeding.

3. Anesthetic effect – lows down the dose of pain relief medicines down to 50-60% in constant use

4. Prevention of complications (30-60%) in acute and subacute periods after injuries, MI, pneumonia, poisoning, renal and hepatic insufficiency down

5. Improving quality of life — lowering number and degree of disability in long-term recovery cases (20-50%) especially in elderly with intolerance to pharmacotherapy

6. Prevention of complications in chronic diseases of gastrointestinal tract, bronchial asthma, hypertension, diabetes mellitus and arthritis

7 Potentiating of pain relief, anti-inflammatory, antihypertensive and some other medicines (30-50% dose decrease)

Areas of medicine where MDM therapy is recommended:

Cardiology: IHD, MI, arrhythmia, CF

Pulmonology: pneumonia, bronchitis, BA

Gastroenterology: stomach and duodenum ulcer, colitis, cholecystitis, pancreatitis

Endocrinology: complications of DM, thyroid and parathyroid glands disorders

Rheumatology: arthritis

Gynecology: inflammatory conditions, dysfunctions

Urology: ED and prostatitis

Neurology: dysfunctions, inflammatory conditions and rehab after strokes

Psychiatry: neuroses, depressions and asthenia conditions

Surgery: preparation and rehab

General medicine: thermal lesions, infections, immunodeficiency, emergency medicine, pediatric medicine

Prevention medicine: low resistance for physical and emotional stress, professional diseases and bad environmental conditions

Sports: rehab after extreme workouts and traumas, increasing of endurance

Professions with extreme overloads (physical and emotional)

3.1. MDM therapy for patients with MI

3.1.1. Acute MI

240 patients hospitalized within 6 hours after disease onset. 100 — control, 140 — MDM-therapy group. Both groups were receiving standard prescribed therapy. From 140 patients 120 were getting 15 days course of daily 30 min MDM treatments, 20 patients received single MDM treatment within first 24 hours. Groups were similar for age and gender differences and initial data.

For evaluation of necrosis size and compensatory hypertrophy of LV precardial carting through 35 leads (P.R.Maroko et.) with estimation of ST amplitude and number of QS complexes for evaluation of ischemic area and dynamics of cumulative amplitude of R-wave for evaluation of compensatory hypertrophy correlating with mass of livable myocardium. Observation was done during hospital stay and 1 year after discharge.

Contractile LV function was measure by phase analysis at “Mingograft-4” (Siemens). Contractile function of RV was evaluated through “Swan-Ganz” catheter, results were recorded by “Mingograf-803”(Siemens). Peripheral blood flow was studied through occlusive plethysmography by “Periquant-3500”(Gutmann). Blood flow was estimated volumetrically and index of peripheral vascular resistance was evaluated.

Gas exchange was defined by “BOC” respiratory monitor for respiratory volume and partial pressure of oxygen and carbon dioxide in arterial blood by “ABL-2(Radiometer) and in expiratory air by “Godart”.

Dynamics of coolagenlike protein in blood reflecting metabolism of collagen was used for evaluation of postinfarction scar formation.

Concentration of hormones and opioid peptides (insulin, cortisole, glucagon, STH, B-endorphin, leucine-enkephalin) was defined by radioimmune method by LKB. Concentration of named hormones was checked on hospitalization, after the first MDM treatment and on 2, 3, 5, 10 and 25-th day of disease. Concentration of B-endorphin and leucine-enkephalin was checked in blood before and after the MDM-treatment at the first day of disease.

Blood from 30 patients with 2-3-d class angina pectoris without MI and DM were examined (empty stomach) in the morning at the second week of hospital treatment.

Results.

No proven differences at size of necrosis, ischemic lesion and number of precardial leads with QS complexes were observed in acute period. No proven differences at concentration of creatine phosphokinase were observed at first 5 days of MI.

Major difference at dynamics in precardial carting as well as voltage increase of QRS complexes (that shows fast development of compensatory hypertrophy of LV wall) (fig.5) between the control and MDM group in favor of MDM group was observed starting on 10-th day. Statistically meaningful smaller number of QS complexes was observed in MDM group 1 year after MI occurrence that can reflect pronounced retraction of post MI scarring.

Fig.5, Erh 35 precardial leads (MDM therapy) fig.6.

Dynamics of summed Rh in                        Concentration dynamics of collagenlike

35 precardial leads im patients                     protein in plasma of patients

with MI (MDM vs control)                          (MDM vs control)

МДМ-MDM

Котроль-control

Год – year; сутки – day; часов (часа) — hours; Время от начала ИМ time after MI onset; мм – mm; мкмоль/мл – mkmol/ml

Increasing of concentration of collagenlike protein between 5-th and 15-th after MI shows faster forming of post MI scar when MDM is used (fig.6) and it is linked with improving of LV contractile function, which was reliably higher in MDM group in subacute and distant periods.

With single MDM treatment normal contractility of both ventricles stayed unchanged and initially low contractility reliably went up. Peripheral blood flow in arm reliably increased and vascular resistance decreased.

Gas exchange index improved as well. With no change in minute respiratory volume and partial pressure of carbon dioxide in arterial blood, oxygen partial pressure reliably increased in arterial blood and alveolar arterial carbon dioxide gradient decreased. Probable pathway of these is improving of permeability of pulmonary membranes and reduction of circulatory hypoxia.

Data obtained from study of indicators of stress intensity and hydro carbonates metabolism shown at table 2. Patients received MDM in first hours of MI manifestation had blood concentrations of glucagon and cortisole reliably (p<0.05) decreased and STH increased, also in comparison to a control group insulin and STH concentrations were higher on 3-5 and 1-5 days of disease respectively and cortisole concentration was lower on 1-3 days.

Table 2:Dynamics of insulin, glucagon, STH and cortisole concentration in blood of patients with MI underwent MDM therapy

Day of

MI

Indicator

Group

1

2

3

5

10

25

of patients

initially

After MDM

INDSULIN

I

28,73,1

32,53,2

31,02,8

35,32,8*

34,82,9*

31,13,0

27,62,9

McU/ml 

II

28,42,7

27,32,8

27,12,4

27,62,4

26,72,7

27,72,7

27,42,5

Glucagon

I

23719,1

18017,4**

17618,3

16515,4

1495,1

1413,8

1354,0

ng/l

II

23116,2

21617,7

19615,1

18414,3

16815,2

1492,5

13611,1

STH

I

1,150,18

2,440,30***

1,910,21*

1,460,19*

1,23,16*

0,820,15

0,89,16

ng/l

II

1,290,12

1,410,14

1,100,11

0,920,09

0,83,10

0,75,11

0,800,09

Cortisole

I

92767,1

61559,3**

68061,2*

65963,4*

54752,0*

5526,9

49348,5

nmol/l

II

88945,2

88544,1

89343,9

85243,0

72741,5

6630,8

5046,8

Group I –group underwent MDM therapy, II-control (At the first day of MI second blood test was done same time for both groups)

*- reliable in comparison to control, ** — reliable changes in comparison to initial data

Results of MDM treatment: concentration reduction for stress-hormones (catabolic) — cortisole and glucagon and growth for STH and insulin (anabolic hormones) considered as positive changes for patients with MI meaning that protein synthesis in myocardium was increasing and proteolysis was decreasing [3,10,11]. It corresponds with better clinical conditions of patients with MI who underwent MDM therapy. Therefore dynamics of concentration changes for those hormones shows stimulation of reparation after MI by MDM.

Blood concentration of B-endorphin end leucine-enkephalin in immediate acute period after MI went up after MDM therapy from 8,7 + 1,5 to 16,3+ 2,8 pmol/l and from 112,5+ 14,1 to 174,7 +26,3 pg/ml (p<0.05) respectively that shows stimulation of opioid system by MDM.

Clinical picture of MI was changing under MDM-therapy as well. On 2-3 days frequency of anginous pain attacks was lower and dose of opioid analgesics was lower. Frequency of arrhythmia particularly of extra systoles was lower and degree of cardiac failure was less, between 4-th and 10-th days these changes were statistically reliable. Recurrence was 10,3%, cardiac aneurisms by echocardiography were diagnosed in 44%, lethality was 10,3% in MDM group vs. 30%, 62,5% and 17,5% in control group respectively, none of MDM group patients died from progressing cardiac failure.

Within a year after MI in MDM group post infarction angina was registered in 60% vs. 91,7 in control group, cardiac failure was diagnosed twice less in MDM group with no recurrent MI (16,7% in control group), 60% patients of appropriate age from MDM group came back to jobs vs. 25% in control group.

Therefore including of MDM treatment into MI therapy had positive impact on clinical picture at all periods of MI with decreasing of frequency of anginous pains, relapse of MI, aneurysm forming, arrhythmia and cardiac failure development. Life quality improves, faster return to work of higher number of patients is due to faster forming of compensatory hypertrophy of LV wall with developing of collateral blood flow.

Stimulation of opioid system of CNS with increase of concentration of circulating B-endorphins and leucine-enkephalins is one of the major factors for faster scar forming with compensatory myocardial hypertrophy accompanied by improved contractility and peripheral blood flow.

When MDM treatment applied within first hours after MI concentration of glucagon and cortisol reliably decreases with simultaneous increase of insulin and STH concentrations. Comparing to the control group of patients group with MDM therapy in acute period of MI had reliably higher concentrations of insulin and STH and lower concentrations of glucagon and cortisol from first till tenth days after MI. Improvement of gas exchange with resulting lesser circulatory hypoxia is another important effect of MDM therapy. Considering lack of negative side effects MDM therapy maybe recommended for virtually all patients with MI.

3.1.2. Postinfarction period.

Results of single and repeated courses of MDM therapy for 162 outpatients who applied for rehab within 2-4 months period after MI. 82 patients underwent MDM therapy and 80 patients were at the control group (table 3).

Table 3

Parameter

MDM group

Control

Total number of patients

82

80

Male

60 (73%)

62 (77%)

Female

22 (27%)

18 (23%)

Average (in years)

54,4 1,2

53,8 1,3

Primary MI

56 (68%)

57 (71%)

Relapsed MI

26 (32%)

23 (29%)

Large-focal MI

49 (60%)

48 (60%)

Intramural MI

33 (40%)

32 (40%)

Concomitant HT

74 (90%)

73 (91%)

Concomitant DM

11 (13%)

9 (11%)

Groups were similar as by clinical conditions of acute period of MI including complications so by therapy applied.

MDM therapy was applied in 1,5-4 months after MI. 10 treatments 30 min each daily with 2 days interruption after 4-5 procedures; in some cases 15 procedures were performed.

MDM therapy average tolerance was good, 5(6%) of patients experienced headaches after first 2 treatments without recurrence afterward; 9(11%) had minor irritation at site of forehead electrode placement disappearing after moisturizer application.

Patients were observed during 1-3 years period, some patients were receiving repeated courses of MDM therapy on quarterly basis; interval between first 2 courses depended of results of the first one and was fluctuating between 1 and 3 months. Distribution of patients by number of treatments received is shown at table 4.

Table 4.

N of courses

1

2

3

4

5

6

7

8

9

10

11

12

N of patients

3

18

14

11

6

5

5

6

4

5

3

2

Results:

  1. Antistress effect. Starting with the first course of MDM therapy 90% of patients reported positive mood change, better appetite and sleep pattern, higher endurance for daily commotions. Meanwhile 60% patients from control reported were suffering from asthenia syndrome and required use of tranquilizers.
  2. Decreased number of complications including relapse of MI (fig-s 7-11)

Fig. 7.

Fig. 8.

Fig. 9.

Fig. 10.

Fig. 11.

Conclusion:

  1. Courses of MDM therapy (single and repeated 10 times courses with 1-3 months interval) were tolerated well by patients with IHD in all periods of MI.
  2. Including of MDM therapy into complex therapy for patients with MI has positive impact at a clinical picture of all periods of MI and post infarction period increasing occurrence frequency of anginous pains, MI relapse, arrhythmia, cardiac aneurysm formation, post infarction angina and improves “life quality” in post infarction period.
  3. Major action of MDM is normalization of opioid and hypothalamic hypophysial systems functioning resulting in stimulation of immediate and long-term adaptation system and Antistress effect.
  4. Considering decrease of angina incidents and MI relapse with faster myocardial compensatory hypertrophy forming faster development of collateral blood flow in ischemic regions may be supposed.

3.2. MDM therapy for patients with HT

3.2.1. Stationary (hospital) treatment of hypertensic crisis

41 patients with the second degree HT hospitalized with HT crisis were studied.

Crisis was treated with standard therapy. 21 patients average 54 years, 52% male, 52% female, 5% — HT III, 95% — HT II formed control group with standard therapy and imitation of MDM therapy. 20 patients 53 years average, 75% male 25% female, 10% — HT III, 90% — HT II additionally to the standard therapy underwent to 10 daily MDM treatments. First treatment performed after crisis was cured.

Groups were similar by anamnesis, clinical picture and by indicators of central hemodynamic.

BP was similar in both groups during the whole stay in hospital and was stable at similar figures at discharge. Clinical picture reliably differed. Headaches, dizziness, angina, shortness of breath lasted for average 2,3 days in MDM group vs. 4,3 days in control. Side effects of pharmacotherapy (collapse, allergies, psychological disorders – 14% in control vs. almost none in MDM group. Total daily antihypertensic drugs consumption was 20% less in MDM group.

Subjectively patients from MDM group noticed better sleep pattern, appetite and emotional stability meanwhile some of the patients from control were refusing MDM therapy imitation finding it “ineffective”.

Possible pathway of MDM effect is change of functioning of opioid system that is one of major antistress systems. Decrease of ACTG production and cortisol concentration in blood may play its role in BP stabilization.

Therefore MDM use in combined therapy of patients with HT after crisis is fixed may bring faster regress of subjective symptoms of hypertensic crisis, less number of side effects of pharmacotherapy with lowering doses of antihypertensic therapy.

3.2.2. Outpatients care.

2 groups of patients with similar initial conditions were studied during 4 years. MDM group (730 patients) were treated by MDM, courses 10-15 times with 1-3 months intervals patients from the control group (700) were receiving all available modern medicines for HT (ACE inhibitors, B-blockers, diuretics, Ca antagonists etc.) table 5.

Table 5.

Parameter

MDM group

Control

Total number of patients

730

700

Male

248 (34%)

252 (36%)

Female

482 (66%)

448 (64%)

Average (years)

48,4 0,3

49,5 0,4

1 stage of HT

87 (12%)

90 (13%)

2 stage of HT

349 (48%)

334 (48%)

3 stage of HT

294 (40%)

276 (39%)

MI in anamnesis

203 (28%)

205 (29%)

IS in anemnesis

69 (9%)

57 (8%)

MI + IS in anamnesis

22 (3%)

14 (2%)

Duration of HT 1-3 years

84 (12%)

76 (11%)

Duration of HT 4-10 years

317 (43%)

324 (46%)

Duration of HT over 10 years

329 (45%)

300 (43%)

Concomitant IHD

651 (89%)

623 (89%)

Concomitant DM

211 (29%)

189 (27%)

Initial BP level 110-140/70-90 mm Hg

182 (25%)

180 (26%)

Initial BP level140-160/70-100 mm Hg

269 (37%)

292 (42%)

Initial BP level 160-180/90-110 mm Hg

255 (35%)

209 (30%)

Initial BP level over 180/110 mm Hg

24 (3%)

19 (2%)

MDM treatment – 30 min daily 10 times up to 15 if needed quarterly, in needed interval between first two courses could be from 1 up to 3 months. Distribution of patients depending on number of courses received is shown at table 6.

Table 6.

# of courses

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

# of patients

73

83

76

70

77

63

62

49

41

26

30

27

24

18

11

28 patients (21 female, 7 male, average age 45,7+1,8 years) underwent MDM monotherapy (without medicines) 30-50 min for hypertensic crisis (75% cerebral, 25% cardiac type).

Some patients were observed on regular basis for over 2 years every 1-3 months – 424 patients from the control and 438 from MDM group. In MDM group 288 patients were getting regular MDM treatments other 150 received 1-7 10-15 times courses.

Vast majority of patients had good tolerance; never the less 36 (5%) complained for headaches after 1-3 procedures, 4 patients (0,5%) stopped treatments for that reason.

Dynamics of BP in hypertensive crisis after a single MDM treatment

Fig. 12

До–Before После МДМ— After MDM

Сист– Systolic Диаст АДDiastoloic BP мм.рт.ст. — mm Hg

Most of those patients had detected by rheoencephalography breached venous drainage due to pronounced osteochondrosis in cervical spine. Most probably these headaches were caused by increased volume of brain due to arterial vasodilatation.

In 23(82%) patients where hypertensic crisis was treated by MDM monotherapy BP went down by the end of the procedure or 10-20 min after (fig.12), in other 5 patients BP stayed unchanged, yet 3 out of these 5 patients reported improving of their conditions despite of BP. BP did not raise in any patient.

After first course of MDM therapy positive dynamics for BP was registered for 619 (85%) of patients (checked at least twice daily). In 93 (13%) of them BP went down after the first treatment and did not went up during the observation period, in 437(60%) – after 3-5 treatments and in 89(12%) – after 6-12 treatments (in later cases course was prolonged up to 12-15 treatments). All these patients reported better sleep, less headaches, less sensitivity to weather changes, higher endurance to physical and emotional stress. Same positive changes were reported by 36 patients with unchanged BP and only 75 (10%) reported no improvement. 42(6%) of patients (mainly under 45 y.o. with HT I without other health problems) came back for the next course of MDM therapy only in 1,5-2 years complaining for rising BP, during that period no medicine for BP was taken.

Stability of BP at lower level was reported by 628 (86%) out of 657 patients receiving MDM treatments on quarterly basis. Despite of lack of positive changes of BP after the first course 38 patients continued receiving treatments, 21 of them showed positive dynamics after 3-6 courses, for others treatments were stopped due to lack of effect. For 12 patients despite of improvement after 1-2 courses later return to initial conditions was reported.

Results of 2 years long study of patients with HT receiving MDM therapy and control (pharmacotherapy) shown at table 7.

 Table7.

Parameter in 2 years of observation

MDM group

Control

Total number of patients

438

424

Typical BP 110-140/70-90 mm Hg

189 (25  43%)

91 (26 21,5%)

Typical BP 140-160/70-100 mm Hg

212 (37  48,6%)

232 (42 54,5%)

Typical BP 160-180/90-110 mm Hg

35 (35  8%)

85 (30 20%)

Typical BP over 180/110mm Hg

2 (3  0,4%)

16 (2 4%)

Complications: IS

7 (1,5%)

20 (4,7%)

Complications: MI

11 (2,5%)

34 (8%)

Complications: Angina pectoris

76 (17%)

153 (36%)

Complications: Cardiac Failure

4 (0,9%)

16 (3,8%)

Complications: Arrythmia

43 (9%)

125 (29,5%)

Mortality

5 (1%)

27 (6,4%)

Regular pharmacotherapy: ACE inhibitors

198 (45%)

368 (87%)

Regular pharmacotherapy: B-blockers

122 (28%)

280 (66%)

Regular pharmacotherapy: Diuretics

151 (34,5%)

327 (77%)

Regular pharmacotherapy: Ca2+ antagonists

36 (8%)

114 (27%)

Regular pharmacotherapy: other antihypertensive m.

17 (4%)

82 (19%)

Figures (25 43%) show dynamics of indicators in 2 years comparing to initial data

As seen from table 7 data BP was stabilized at WHO recommended level for reliably bigger number of patients from MDM group comparing to control, number of complications and clinical picture was different in favor of patients from MDM group as well with two-three times less medicine consumption.

Conclusion.

  1. MDM therapy is tolerated well by patients with HT. Side effects except transient headaches (5%) were not detected.
  2. MDM treatment can be used as emergency treatment in hypertensic crisis as the only therapy and improves results when used in combined hospital care for HT patients.
  3. Quarterly courses of MDM therapy (10-15 times) may be recommended for ambulatory care combined with pharmacotherapy for patients with HT with 2-3 times decrease in medicines consumption and therefore with less side effects.
  4. Probable pathway of MDM therapy is stimulation of endogenous opioid system that neutralizes negative workload at CNS (stress, environmental factors etc).

3.3. MDM treatment as a component of a combined therapy for BA.

MDM therapy has been successfully used for last 20 years for treatment of different respiratory system disorders (BA, COLD etc.).

30 patients hospitalized during acute period of BA were observed. 15 patients were getting MDM treatments together with standard therapy, 15 patients – control group – only standard therapy. 8 female and 7 male patients in each group, severity of disease according to GINA 2006 and type of BA are presented in tables 8 and 9

Table 8. Distribution of BA by severity

Severity

MDM group

Control

Light persistive

2

1

Medium

8

8

Heavy

5

6

Table 9. Distribution of BA by type

MDM group

Control

Atopic

2

1

Endogenic

5

6

Mixed

8

7

Idiosyncratic

1

All patients were hospitalized with medium severity of BA with respiratory frequency up to 30 per min, percussion “box” sound and auscultative weaken harsh breath with whistling wheezes

Standard therapy was based on GINA 2006 recommendations and consisted of bronchial spasmolytic, inhalation glucocorticoid. In MDM group patients additionally received 10 MDM treatments 30 min each 1mA.

MDM group patients showed positive dynamics (average): severity went down to satisfactory in 3,2+0.31 days, shortness of breath disappearance – 3,8+0,8 days. Percussion sound came back to normal in 6,3+1,47 days, auscultative vesicular breathing appeared in 7,6+1,69 days, dry wheezes disappeared in 8,1+1,76 days, in 2 patients residual wheezes remained till the end of MDM therapy course. In control dynamics was such (same order respectively): 3,9+0,4, 4,0+0,97, 7,4+1,51, 8,2+1,51, 9,2+0,74.

MDM therapy was tolerated well.

13 patients had elevated IgE level initially (7 patients from MDM grout and 6 from control). MDM group patients initially had average IgE level 171+42,3 ME/ml. 5 patients showed insufficient dynamics (IgE level drop only up to 10%) 2 patients showed drop 23 and 45%, by the end of MDM therapy average IgE level was 109+31,2ME/ml, in control average IgE level went down from 132+21,7 to 118+19,0ME/ml.

13 MDM group patients initially had decreased FEV (average 67,+8,2%, after MDM therapy 9 patients had shown normal FEV, 3 patients have improved FEV average FEV became 87,6+7,1%.

13 control group patients had average FEV 66,4+12,5% by the end of therapy 7 patients achieved normal FEV, 3 patients had improved FEV average FEV became 81,1+12,9%. Therefore patients from MDM group have shown more pronounced tendency for reconstruction of bronchial potency.

PEV was checked on 1-st,5-th and 10-th days and found comparable, MDM vs control respectively: 270+43, 347+39, 362+38 and 282+50, 326+42,349+39 l/min. Positive dynamics was noticed earlier for MDM group patients though, normal numbers for PEV were reached on 3-d day for MDM group patients unlike slower improvement in control. Hospital stay for MDM group patients was 16,1+1,8 days vs 17,6+1,5 days for control.

Conclusion.

MDM treatment may be recommended as an efficient and safe component of combined therapy for BA. Though not all obtained data were statistically proven but tendency for earlier general improvement was obvious.

Positive impact of MDM at respiratory functions including gas exchange is due to change of neuro hormonal and immune status.

3.4. MDM for neurology and psychiatry.

In 1992-1993 in Moscow Center for speech and hearing disorders 130 patients (42 adults, 64 children 3-6 y.o. and 24 children 7-15 y.o.) underwent 10 times course of MDM therapy for neurosis and speech disorders due to organic and functional pathologies.

In 1992-2000 in Moscow Specialized Hospital #8 named after Soloviev 5000 patients underwent MDM treatment for depression, hypochondriac neurosis, vascular neurosis-like conditions, asthenia and hysteria types of neurosis.

In 1997-2002 in Moscow outpatients clinic #185 452 patients (293 female, 159 male average 48+0.5 y.o.) underwent MDM therapy for following diseases (table 10):

Table 10.

Disorder

# of patients

# of MDM courses

1

2

3

4

5

6

Osteochondrosis with radicular syndrome

382

90

35

36

30

32

27

Neuritis (facial, lumbar nerves and radiculitis)

38

36

2

Dyscirculatory encephalopathy

127

41

19

22

15

18

12

Post stroke conditions

25

9

5

3

3

2

3

Neuroses

54

6

9

10

11

10

8

Some patients had combined disorders (ex. Dyscirculatory encephalopathy typical for patients with cervical osteochondrosis)

In 2001-2002 17 patients 15-26 y.o. (average 17,4) with alcohol (12) and heroin (5) dependency were observed in Moscow Psychiatry Research Institute. Later group were in stage of acute post abstinent disorder with depressive behavioral changes. All patients underwent MDM therapy and for later group psychotropic medicines (antidepressants, light neuroleptics) were used.

In 2000 4 patients with ICP (spastic diplegia) and 6 patients after serious CCT 8-15 y.o. underwent MDM therapy in the Pediatric Research Institute of Russian Academy of science. And Stimulation of adaptation system, tolerance to rehab workload stability of vegetative and hemodynamic systems was studied.

Results and discussion.

Outpatients clinic #185: good tolerance to MDM therapy was shown; pinching and burning sensation in sites of electrode placements within first 5-10 min was reported. 38 (8,4%) patients were reporting short (1-4 hours) headaches after 1-3 treatments that was a reason for 5 patients to stop therapy. In all cases encephalogram showed slow venous outflow with simultaneous arterial vasodilatation that resulted in increase of brain volume that could be a reason for headache.

365(80,7%) patients showed positive dynamics other stayed unchanged. Pain syndrome decreased or disappeared, neurological status, physical activity, sleep and appetite improved; quantity of medicines taken decreased 30-80%. 52(14%) patients with osteochondrosis reported transitory increase of pains in first 2-4 days. Pain syndrome decreased after 1-4 treatments in patients with radiculitis and neuritis. Results of MDM therapy for vascular encephalopathy were in reverse proportion to intensity of arteriosclerosis of brain vessels. Recovery after AIS was faster in 19 (76%) of patients in reverse proportion to time after AIS. Patients with asthenia-depressive neurosis reported subjective improvement after 2-6 treatments particularly after use of triangle impulses (91%).

Advantage of MDM therapy is broad spectrum of effects for combined pathological conditions. Most of patients additionally to neuro and psychiatric disorders had HT, IHD including MI in anamnesis, stomach and duodenum ulcers, rheumatic fever, hemodynamic failure etc. MDM therapy had positive impact for all named diseases that resulted in decreasing of quantity of medicines taken.

Data obtained in Center for speech and hearing disorders for kids with retarded speech development due to organic brain disorders showed 20% better results when MDM therapy was added to a standard therapy. Regardless of age higher endurance, less anxiety level and better sleep were achieved for patients with neurosis and neurosis-like conditions.

Very good results of use of MDM treatment were obtained in Clinic for Neurosis named after Soloviev. Clinical improvement was observed in 90-95%, stay in clinic decreased in 1.5 times, clinical efficacy was 2-3 times higher comparing to other method of electrical stimulations.

In Moscow Psychiatry Research Institute following results were obtained for 12 patients with alcohol dependency after the very first MDM treatment: anxiety level, pulse, elevated BP and breathing frequency went down, skin pink color returned. After course of MDM therapy patients have reported subjective feeling of “inner peace” and predetermined further continuation of MDM therapy.

5 patients with drug dependency after 3-5 MDM treatment experienced reduction of asthenia and by the end of course better behavioral pattern and sleep with less nightmares more pronounced then in case of use standard therapy without MDM.

Research Pediatric Institute RAS studied patients with cerebral palsy and condition after heavy craniocerebral trauma for topographic distribution of level of omnipresent potentials (LOP) (sum of membrane potentials of different brain cells)– one of major electrophysiological indicators of CNS activity showing metabolic intensity in the whole brain and its regions.

All patients showed gradual forming of sc. “dome-like” pattern of distribution of LOP with typical absolute and relative gradients for five studied brain zones close to normal distribution. This dynamics was more evidenced in patients after CCT comparing to patients with ICP.

Conclusion.

1.Neurology and psychiatry patients showed good tolerance to MDM-therapy. Side effects (except transient headaches due to breached venous drainage and transient aggravation of pain syndrome in patients with osteochondrosis) were not detected within 2 years of observation.

2.76-90% of patients with radiculitis, neuritis, conditions after stroke, neurosis and speech pathology underwent MDM therapy showed positive clinical dynamics and reduction of medicines quantity.

3.MDM therapy maybe recommended for broad use for neurology and psychiatry practice.

4.High efficiency of MDM therapy proven for patients with neurosis of different genesis.

5.MDM monotherapy for patients with alcohol dependency and as part of combined therapy for heroin dependency allows faster reduction of behavioral disorders and somatovegetative state

6.Positive dynamics of regional and whole brain metabolic processes evoked by MDM therapy detected as changes of topographic distribution of LOP shows deep changes of brain activity. That explains evidence long duration of clinical effects of MDM therapy.

3.5. MDM for Endocrinology.

High efficiency of MDM treatment as part of combined therapy was shown for type II DM with fast stabilization of blood glucose in case of decompensation and reduction of glucose lowering medicine with 40% of cases of switching from insulin injections to tablets.

Positive dynamics was achieved for patients with complications of DM reduction of pain and clinical improvement in polyneuropathy, improving of renal function in case of failure and improving of microcirculation with some clinical improvements in case of trophic ulcers.

Even better results were achieved for patients with type I of DM, lowering of insulin dose after first course of treatments in most cases.

Positive clinical dynamics observed for patients with thyroid gland dysfunction (nodular goiter and autoimmune thyroiditis). After 2-3 10 treatments courses of MDM therapy thyroid gland function was improved, nodes became smaller (by ultrasonic examination), dose of medicine taken decreased and number of antibodies lowered for 2-3 months period in case of autoimmune thyroiditis.

3.6. MDM for Pediatric patients.

Adaptation system in children is different from one in adults by higher lability and adaptation potential, therefore clinical efficacy of MDM therapy is much higher for children comparing to adults at most.

MDM is used for treating of BA, allergies (atopic dermatitis), neurosis (including speech disorders), injuries, burns etc.

 3.7. MDM for Sports Medicine.

There are special (trainings) and general means for improving of specific endurance in modern sports of high level. Considering high individuality of each sportsman working at extreme workloads MDM therapy should be designed for each case individually.

There are 6 regulatory levels for functional systems of human body: molecular, subcellular, cellular, organic, systemic and of the whole organism. They all linked by reciprocal influence with impact of higher structures by means of hormones and regulatory peptides through intracellular and molecular pathways to target organs and systems. Theory behind MDM therapy is based on idea of integrity of adaptation to stress factors connected to extreme physical workloads for professional sportsmen.

Neuro endocrine system activation improves quality of adaptation response at all regulatory levels that brings up results in sports and brings down intensity of injuries due to physical overloads.

Efficacy of MDM therapy for sports is being studied since 1990. First time it was used for preparation of Russian swimming team in 1991 for the World Championship and then 1992 for Olympic games. MDM therapy was performed in double numbers of treatments every 2-3 months for a year.

Intensification of metabolism and higher level of B-endorphins improved stress tolerance, increased intensity of trainings, shorten recovery period resulting in high results in competitions.

Achieved level of concentration of B-endorphins with raised pain threshold was proportional to achieved results in sports.

Same data was received for other sports they can be described as following:

  1. Higher training effectiveness and final results due to higher potential of adaptation response

  2. Higher tolerance to stress related to overloads

  3. Shorter recovery period

  4. Prevention of common flu caused by immune system impairment due to stress reactions to overloads

  5. Improvement of psychological status with higher tolerance to emotional stress

  6. Better and faster recovery after injuries.

Therefore MDM therapy, based on increasing of reconstructive and preventive abilities of a human organism through modulation of adaptation response by stimulation of neuro endocrine system, is an effective method for preparation of professional sportsmen.

3.8. MDM for chronic fatigue syndrome.

Modern lifestyle saturated with information flows, city noise and other harmful environmental factors leads to constant overload of CNS, that suppress neuro endocrine functions and therefore adaptation abilities of an organism. That brings formation of CFS that consists of less tolerance to daily stress, sleep disorders, headaches etc that subsequently speeds up aging process.

MDM therapy for stress overloads leads to less tension, better attention, faster reactions and higher capacity for work.

Therefore MDM therapy may be recommended for generally healthy people working in stressful conditions or in professions requiring constant alertness (dispatcher, security etc). Quarterly 10 treatments MDM courses improve tolerance to external negative factors, preventing development of chronic diseases and probably prolonging life (based on hypotheses of V.M.Dilman).

Combination of improved quality of life and virtual lack of side effects, including distant ones makes MDM therapy a powerful method for a broad use.

CONCLUSION.

THIS ARTICLE PRESENTS NEW METHOD OF TRANSCRANIAL ELECTROTHERAPY FOR CORRECTION 
OF ADAPTATION SYSTEM AND INCREASING OF ADAPTATION POTENTIAL OF A HUMAN ORGANISM. 
MDM INFLUENCES AT NEURO ENDOCRINE CENTERS LOCATED IN MESENCEPHALON AND DIENCEPHALONS 
BRAIN STRUCTURES.