MOHAMED A. SABBAHI, FIKRIYE OVAK, SELDA UZUN, YESIM SENGUL PERCUTANEOUS SPINAL CORD STIMULATION & RECORDING MULTISEGMENTAL MOTOR RESPONSES (MMR) IN UPPER & LOWER LIMBS: A POTENTIAL PROCEDURE FOR TESTING SPINAL CORD INJURIES & DISEASES. MOHAMED A. SABBAHI, FIKRIYE OVAK, SELDA UZUN, YESIM SENGUL TEXAS WOMAN’S UNIVERSITY, SCHOOL OF PHYSICAL THERAPY; & TEXAS ELECTROPHYSIOLOGY SERVICES, HOUSTON, TEXAS.

What is MMR? -Multisegmental Motor Responses Percutaneous -Electrical stimulation of the spine at the Cervical and Thoracic vertebral levels while recording upper and lower limb muscular signals from proximal and distal limb muscles.

CMMR: Cervical Multisegmental Motor Responses Craniovertebral Junction C3 C7 Upper and Lower MMR

TMMR: Thoracic Multisegmental Motor Responses T11-12 Upper and Lower MMR T1 and T9 L1-L2

Previous & Other studies ???????????????

R_L Limb dominance and the fact that right and left limbs may contain muscles with different levels of strength due to training as well as differences in functional use may cause signal asymmetries in healthy and injured subjects (7-10).

How MMR is related to H-reflexes?

H Reflex& MMR Recent report suggested that MMR is similar to the H reflexes, maybe considered to be a central version of the H reflexes Our studies with MMR showed substantial differences between the H reflexes and MMR.

Signal amplitudes increases with increased stimulus intensity Similarities and differences between H reflexes and MMR in healthy subjects and SCI patients. Signal amplitudes increases with increased stimulus intensity Latencies were fixed and increased with distance of the muscle from the spinal cord

Differences between H reflexes and MMR H reflex could be recorded from Sol, VMO & FCR muscles only MMR could be recorded from all upper and lower limb muscles H-reflex amplitude decreased during standing (loading) as compared to lying position, whereas the MMR is facilitated Latencies of MMR are almost 0.5 of H reflexes. Muscular responses of MMR could be recorded from both upper and lower limb simultaneously with single stimulus at C7 or T11, dissimilar to reflex pathways.

Similarities and differences between H reflexes and MMR in SCI patients. In chronic SCI patients, both H reflex and MMR may be depressed simultaneously However with increased excitability of the nervous system both H-reflex and MMR may be facilitated.

METHODS- STIMULATION & RECORDING T11-12 vertebral segment was electrically stimulated using surface electrode (stimulation parameters: 1 msec .,0.2 PPS, at maximum responses). C7 Cervical spinal segment was also stimulated using similar stimulation parameters the MMR of the upper and lower limbs were recorded during both stimulation conditions. Gain: 1000-2000 µv.

SUBJECTS C7-R-SOL-AMP-SIT C7-L-SOL-AMP-SIT T11-R-SOL-AMP-SIT T11-L-SOL-AMP-SIT SOL-H-REF-R-AMP SOL-H-REF-L-AMP C7-R-SOL-LAT-SIT C7-L-SOL-LAT-SIT T11-R-SOL-LAT-SIT T11-L-SOL-LAT-SIT SOL-H-REF-R-LAT SOL-H-REF-L-LAT J.S 118.22 N/A 58.05 194.05 23.05 25.84 18.69 20.01 S.A 15 30 100 125 650 22 18 20 34.34 33.94 A.P 275 145 290 175 900 3000 17 32.13 31.73 A.M 185 160 1700 1400 15.5 15.1 27.73 27.71 M.Pl 245 1450 365 19 J.R 295 255 305 330 670 1350 23.5 21 34.4 34.64 R.R 75 82 85 1150 4950 37.75 37.45 M.G NR H.L.G R.S J.O.H 110 2950 31.12 31.83 G.G 61.94 37.14 78.64 191.6 653.23 296.98 20.74 19.14 20.46 36.51 68.17

Signal was recorded, using surface electrodes, from the upper extremity muscles (APB, FCR, BB, Triceps) as well as the lower limb muscles (VMO,MH, SOLEUS, TA.). Recording set-up: fig. (1)

The nerves of the spinal cord are divided into five levels The nerves of the spinal cord are divided into five levels.  (Illustrations by Kathryn Born)

Spinal nerves emerging from the spinal cord through the intervertebral foramina with muscles or muscle movements listed for specific levels. From McQuillan et al., 2002.

• Anterior median fissure — separates anterior funiculi, • Posterior median sulcus — divides posterior funiculi

Gray Matter and Spinal Roots • gray matter consists of soma, unmyelinated processes, and neuroglia • gray commissure — connects masses of gray matter; encloses central canal • posterior (dorsal) horns — interneurons • anterior (ventral) horns — interneurons and somatic motor neurons • lateral horns — contain sympathetic nerve fibers

Organization of Gray Matter • dorsal half — sensory roots and ganglia • ventral half — motor roots • dorsal and ventral roots fuse laterally to form spinal nerves • four zones are evident within the gray matter — somatic sensory (SS) visceral sensory (VS) visceral motor (VM) somatic motor (SM)

Cross-Sectional Anatomy of the Spinal Cord

White Matter in the Spinal Cord • fibers run in three directions — ascending, descending, and transversely • divided into three funiculi (columns) — posterior, lateral, and anterior • each funiculus contains several fiber tracks fiber tract names reveal their origin and destination fiber tracts are composed of axons with similar functions

White Matter: Pathway Generalizations • pathways decussate • most consist of two or three neurons • most exhibit somatotopy (precise spatial relationships) • pathways are paired (one on each side of the spinal cord or brain)

Segmental Spinal Cord Level and Function C1-C6 Neck flexors C1-T1 Neck extensors C3, C4, C5 Supply diaphragm (mostly C4) C5, C6 Shoulder movement, raise arm (deltoid); flexion of elbow (biceps); C6 externally rotates the arm (supinates) C6, C7 Extends elbow and wrist (triceps and wrist extensors); pronates wrist C7, T1 Flexes wrist

Segmental Spinal Cord Function Level T1 -T6 Intercostals and trunk above the waist T7-L1 Abdominal muscles L1, L2, L3, L4 Thigh flexion L2, L3, L4 Thigh adduction L4, L5, S1 Thigh abduction L5, S1, S2 Extension of leg at the hip (gluteus maximus) Extension of leg at the knee (quadriceps femoris) L4, L5, S1, S2 Flexion of leg at the knee (hamstrings) Dorsiflexion of foot (tibialis anterior) Extension of toes Plantar flexion of foot Flexion of toes

Pathways & circuitries tested by MMR (Human & animals)

Ascending pathways anterolateral (nonspecific ascending) pathways lateral and anterior spinothalamic tracts medial lemniscal system (specific ascending pathways) dorsal white column fasciculus cuneatus fasciculus gracilis anterior and posterior spinocerebellar tracts

Descending pathways pyramidal system lateral and anterior corticospinal tracts extrapyramidal system tectospinal tracts vestibulospinal tracts rubrospinal tracts anterior, medial, and lateral reticulospinal tracts

STUDIES IN HEALTHY SUBJECTS Subjects were excluded if they had a history of neck, back, limb pain, or a history of metabolic, neurological diseases (including radiculopathy), arthritis or any form of cancer diagnosis within the past 12 months and if they were obese (BMI>30). Subjects were able to tolerate strong ES to the cervical or thoracolumbar spine.

CMMR FOR UPPER EXTREMITIES

TMMR for Upper Extremities:

The amplitude (left panel) and latency (right panel) of the CMMR and TMMR for different Right Lower Limb muscles .

Mean±SD MMR stimulus intensity threshold levels of CMMR and TMMR for both Upper Limbs.

CMMR For Lower Extremities

TMMR For Lower Extremities

Sample traces of Right:C7 Right Lower extremity ,Left:T11 Right Lower extremity

The amplitude (left panel) and latency (right panel) of the CMMR and TMMR for different Right Lower Limb muscles .C7 (hatched) and T11-12 (solid stimulation.

CMMR and TMMR stimulation thresholds for Right Lower Extremity

Effects of Body Posture on Multisegmental Motor responses in the upper and lower limbs of Healthy subjects.

Multi segmental motor responses for cervical (CMMR) and thoracolumbar (TMMR) have been recorded in the upper and lower limbs of healthy subjects. However, the effects of different body postures have not been studied.

The Purpose: To evaluate the changes in CMMR & TMMR in different body postures. It is hypothesized that testing MMR in different body postures will show the optimal testing method for neurological disorders.

8 healthy subjects Females: (3) Males: (5) Age range (42.5±13.6).

METHODS STIMULATION & RECORDING CERVICAL: Stimulation: C7 vertebral site (1 msec., 0.2pps @ response max.)- surface electrodes Recording:(R UE) Sitting and lying positions. APB, FCR, Biceps, Triceps (surface electrodes). Reference:Shoulder Ground: Acromion. Recording: (R LE) Sitting, Standing and Lying positions: for VMO, TA, Soleus, MH Reference: ASIS Ground : Head Of Tibia THORACOLUMBAR: Stimulation: T11-12 vertebral site (same stim. Parameters) Recording (R UE) same as cervical MMR. Recording : (R LE) Sitting , Standing and Lying positions for VMO, TA, Soleus, MH

1.Sign informed consent form (TWU approved) 2.Testing cervical MMR for Right UE and LE . 3.Testing Thoracolumbar MMR for UE and LE. 4.Subjects were tested for UE while sitting and lying positions and for LE sitting, standing and lying positions.

Averaged 5 traces Dependent Parameters: Peak-to peak amplitude Deflection latency Statistics: Descriptive analysis

C7 & T11 MMR for the Upper limbs were tested during lying and sitting positions. C7 and T11 Lower limbs MMR were tested during in lying, sitting and standing positions.

Signal amplitude was larger in the distal more than proximal limb muscles in the upper limbs; in the antigravity muscle > pogravity muscles in the lower limb and. No significant change in signal latencies was recorded with body postures.

Signals showed robust signal amplitude in the upper limbs with C7 and T11 stimulation. Signal amplitude was higher (by 133 %) during sitting than lying positions for C7 and T11 upper limb MMR (by 135.4%).

There were no significant differences of amplitude values between two different positions (sitting & lying) stimulation recording from upper extremity muscles (p>0.05).

Comparison Posture effect between C7-T11 Upper Extremity MMR

Robust signal amplitude in the upper limbs with C7 and T11 stimulation, Robust lower limb signal amplitude with T11 stimulation, Small lower limb signal with C7 stimulation.

There were no significant differences of amplitude values between two different positions (sitting & lying) stimulation recording from upper extremity muscles (p>0.05).

CMMR for the lower limbs showed higher amplitudes during (by 160%) standing > sitting or lying positions.

Lower limb-TMMR showed higher amplitudes (by 106-200%) during standing>lying > sitting positions.

Signal amplitude was larger in the distal more than proximal limb muscles; In the extensors > flexors in the lower limb In the flexors > extensors in the upper limbs. No significant change in signal latencies was recorded with body postures

No significant differences between three postures (sitting, standing and lying) with C7 stimulation for recording lower extremity muscles. (p>0.05) . T11 Lower limb MMR showed statistically significant increase in the amplitude of Soleus muscle during standing versus lying & sitting (p=0.048). No significant differences were recorded in the other leg muscles (VMO, MH, and TA) (p>0.05).

Discussion: The MMR facilitation of lower limb signal during standing and upper limb signal during sitting are probably due to loading effect that engage the central nervous system in function especially in the extensor > flexor muscles.

Clinical relevance: Optimal testing of patients with neurological disorders should be carried out during loading (standing) > unloading. A comparison of testing results during loading and unloading could be clinically useful for evaluating spinal cord circuitries.

REFERENCES FOR POSTURAL CHANGES OF MMR Sabbahi M, Sengul Y. Cervical Multisegmental Motor Responses In Healthy Subjects. Spinal Cord (Spinal Cord,50(6);432-9,Jan 2012).   Sabbahi M, Sengul Salik Y. Thoracolumbar Multisegmental Motor Responses In The Upper And Lower Limbs In Healthy Subjects. Spinal Cord 49, 741-748, 2011 Similarities And Differences Of The Soleus And Gastrocnemius H-reflexes During Varied Body Postures, Foot Positions, And Muscle Function: Multifactor Designs For Repeated Measures. Alrowayeh HN,Sabbahi M.A,Etnyre B. BMC Neurology.2011 Jun2;11:65

EFFECTS OF LIMB DOMINANCE ON MMR Limb dominance and the fact that right and left limbs may contain muscles with different levels of strength due to training as well as differences in functional use may cause signal asymmetries in healthy and injured subjects.

Similarities CMMR and TMMR procedures have similarities and differences in the technical aspect of the methods (electrode set-up, stimulation levels and noxious sensation) and signal presentations (amplitude, action potential shapes and latencies).

. The MMR signal amplitude in upper limb muscles to C7 and T11 stimulation were comparable. The MMR signal amplitude in lower limb muscles to C7 and T11 stimulation were significantly different showing larger amplitude for the latter and smaller amplitude for the former (C7 stimulation).

C7 can be located by palpation of the cervical spinal process Similarities and differences in methodology Both cervical and thoracolumbar MMR requires superficial electrical stimulation at C7 and T11-12 intervertebral space levels. C7 can be located by palpation of the cervical spinal process T11-12 stimulation site is a challenging procedure with regard to identification of the stimulation site.

In cervical spinal stimulation, the anode should be applied on the acromion of the shoulder on the ipsilateral side of recording the MMR. In thoracolumbar procedure, the anode should be applied on the anterior superior iliac spine (ASIS) on the ipsilateral side of recording the MMR.

In both cervical and thoracolumbar stimulation a large (2 In both cervical and thoracolumbar stimulation a large (2.5” x5”) self- adhesive electrode was found to be more effective in eliciting a large amplitude MMR signal than 2 x2” electrode. Optimization of recording set-up for cervical and thoracolumbar MMR will be the focus of future study.

C7 stimulation evoked large amplitude motor responses in the muscles of the upper limbs (in the millivolts range)

C7 also evoked small motor responses in the VMO, soleus and Tibialis Anterior of the lower limbs (in the microvolts range) MUSCLES MEAN±SD µV Vastus Medialis Obliques 0.8±0.5 M. Medial Hamstring 0.3±0.3 M.Soleus 0.6±0.9 M. Tibialis Anterior 0.2±0.1 C7 RIGHT LEG AMPLITUDES IN STANDING POSTURE

T11-12 stimulation evoked large amplitude motor responses in both lower limbs and upper limbs (in the millivolts range) T11 UPPER LIMB

Reliability and Comparison of Multi segmental Motor Responses in the upper extremity of healthy subjects M.Sabbahi, S.Uzun, F. Ovak –Bittar, Texas Woman’s University, School of Physical Therapy, Houston, Texas and Texas Electrophysiology Services, Houston, Texas

INTRODUCTION Multi segmental motor responses (MMR ) have been recorded in the upper and lower limbs. However comparison between right and left limbs has not been studied. Also reliability of testing these responses in different days has not been reported.

PURPOSE OF THE STUDY This report will present a comparison study between the right and left upper and lower limbs with stimulation of the T11-12 spinal segment. This report will also present the reliability of these MMR when tested at different days.

METHODS- SUBJECTS Healthy subjects: N= 21 (Females: 11, Males: 10) Age : 31 + 10.4 Testing position: sitting or standing.

EXPERIMENTAL PROCEDURES 1. C7 stimulation while recording MMR from the upper limb muscles. 2. T11-12 stimulation while recording MMR from upper limb muscles. 3. T11-12 stimulation while recording MMR from lower limb muscles. 3. Repeat step 1- 3 in a different day.

Dependent & Independent Parameters The peak-to-peak amplitude and deflection latency were the dependent parameters. MMR of all muscles from the right and left, upper and lower limbs were compared (limb side). Also data from first and second days were correlated (test- retest reliability) Stimulation threshold and intensity (current) for maximum MMR amplitude were recorded. The VAS for C7 & T11-12 stimulation were recorded

ANALYSES Five traces were recorded & averaged for each muscle at every trial. Measure peak-to-peak amplitude & latency. Pearson correlation co-efficient rho- between day 1 & day 2 using SPSS-19 package. Compare upper limb signal to C7 & T11-12 stimulation using t-test. Compare stim. Threshold & for Amp. Max. for C7 & T11-12 (1st. & 2nd. Day)

RESULTS Results showed that the MMR of the right and left upper and lower extremities are comparable between limbs in all subjects. Results also showed that signal were not statistically different between day one and day two in the subject’s group. C7 MMR requires a little higher stimulation intensity than T11-12 MMR.

R & L UE Muscles 1st day (Amp: Mean+ SD) 2nd day (Amp: Mean+ SD) APB- R 10±4.5 9.8±5.2 APB- L 8.9±4.7 8.5±4.6 FCR – R 5±2.3 4.9±3.1 FCR – L 5.3±3.6 4.8±3.5 Bi- R 7.6±3.9 6.4±3.8 Bi- L 7.1±4.1 6.6±3.4 Tri- R 6.2±3.4 6.8±4.4 Tri - L 5.9±2.8 6.3±4.4 Table: C7 Upper Extremity 1st and 2nd day MMR Amplitudes.

.000 MUSCLES C7 UE amp Correlations R UE 1st vs 2nd L UE 1st vs 2nd 1st day R vs L 2nd APB Pearson Correlation Sig. ( 2- tailed ) .881** .000 .859** .858** .778** .001 FCR .702** .004 9.1** .729** .002 .960** BI .596* .019 .737** .750** .527* .044 Triceps .829** .452 .091 .839** .831** Table: C7 Upper Extremity MMR Amplitude Correlations

R & L UE 1st day 2nd day APB R 10.8±2.1 11.1±2.3 APB L 10.5±2.5 11.1±2.4 FCR R 7.7±0.8 7.9±0.8 FCR L 7.7±1.2 7.8±0.9 Bi R 5.3±0.7 5.2±0.7 Bi L 5.1±0.7 5.3±0.6 Tri R Tri L 5.3±0.8 Table : C7 Upper Extremity MMR Latency (1st day & 2nd day)

** Correlation is significant at the 0.01 level ( 2 tailed ) C7 UE MUSCLES LATENCIES CORRELATIONS   C7 R UE 1st vs. 2nd C7 L UE C7 UE 1ST R vs L C7 UE 2nd R vs L APB Pearson Correlation Sig. (2-tailed) .737** .002 .844** .000 .944** .929** FCR .690* .004 .870* .707* .003 .764* .001 BB .724* . .862* .772* .899* TB .887* .838* .896* .879* ** Correlation is significant at the 0.01 level ( 2 tailed ) *Correlation is significant at the 0.05 level ( 2 tailed )

T11 R & L UE MUSCLES 1st day 2nd day APB- R 9.8±4.7 9.5±5 APB –L 8.3±4.4 8.5±3.7 FCR- R 4.4±2.3 4.7±2.8 FCR- L 4.6±2.8 5±3.1 Bi - R 4.3±3 3.8±2.8 Bi - L 4.6±3.5 4.6±3.2 Tri - R 5.2±4.2 6±4.2 Tri - L 5.3±3.7 6.3±4.5 T11- R &L UPPER EXTREMITY AMPLITUDE,1ST & 2ND DAY

** Correlation is significant at the 0.01 level ( 2 tailed ) T11 UE MUSCLES AMPLITUDES   T11 R UE 1st vs. 2nd T11 L UE T11 UE 1ST R vs L T11 UE 2nd R vs L APB Pearson Correlation Sig. (2-tailed) .827** .000 .853** .788** .817** FCR .937** .941** .880** .929** BB .862** .891** .925** TB .802** .826** .581* .023 .921** ** Correlation is significant at the 0.01 level ( 2 tailed ) *Correlation is significant at the 0.05 level ( 2 tailed )

R & L UE 1st day 2nd day APB- R 10.7±2.3 10.9±2.3 APB- L 10.5±2.6 10.6±2.4 FCR- R 7.2±1.5 7.3±1.6 FCR- L 7±1.4 7±1.5 Bi- R 5.1±1.5 5±1.5 Bi- L 5±1.6 Tri- R 4.9±1.6 4.6±1 Tri - L 4.7±1.7 T11 R & L Upper Extremity MMR Latencies

T11 LEFT UE MMR LATENCY MEAN ± SD T11 RIGHT UE MMR LATENCY MEAN±SD

** Correlation is significant at the 0.01 level ( 2 tailed ) Muscles Correlations R UE 1st vs. 2nd L UE UE 1ST R vs L 2nd R vs L   APB Pearson Correlation Sig. (2-tailed) .981** .000 .948** .953** .928** FCR .888** .885** .869** .819** BB .952** .976** .960** .961** TB .931** .982** .984** .882** ** Correlation is significant at the 0.01 level ( 2 tailed ) *Correlation is significant at the 0.05 level ( 2 tailed ) Table : T11 UE Muscles MMR Latencies Correlations For 1st And 2nd Day

C7 STIMULATION THR-MAX Amp. 1ST DAY 2ND DAY THR_R 1 38.7 ± 9.4 41.1 ± 10 THR_L 1 39.06 ± 10.4 40.8 ± 10.3 C7_Max AMP._R 1 96.6 ± 11.4 94.7 ± 13.03 C7_Max AMP. L 1 95.7 ± 11.7 95.3 ± 11.6 Table : C7 UPPER EXTREMITY STIM. THRESHOLD AND STIM. FOR MAXIMUM AMPLITUDE OF MMR

Fig : C 7 UPPER EXTREMITY STIM. THRESHOLD AND FOR MAX. AMPLITUDE (MMR)

Current Correlations R- UE 1st vs. 2nd L- UE UE 1ST R vs L 2nd R vs L Threshold Pearson Correlation .901** .865** .881** .960** Sig. (2-tailed) .000 Maximum Amplitude .905** .992** .966** .993** Table : C7 Upper extremity Stim. Threshold and Maximum Amp. for 1st and 2nd day

T11 UE THR- MAX AMP. (MA) 1ST DAY 2ND DAY THR Right 52.5±14 51±12.3 THR Left 53.2±14.3 52±13.4 Max-Right 1 96±10.7 Max_Left 1 96±8.7 96±9.4 Table : T11 UE MMR STIM. THRESHOLDS AND for MAXIMUM AMPLITUDE IN DAY 1 AND DAY 2

** Correlation is significant at the 0.01 level ( 2 tailed ) Current Correlations R- UE 1st vs. 2nd L- UE UE 1ST R vs L 2nd R vs L THRESHOLD Pearson Correlation Sig. (2-tailed) N .822** .000 .925** .953** .909** Maximum Amplitude .929** .978** .971** .991** ** Correlation is significant at the 0.01 level ( 2 tailed ) *Correlation is significant at the 0.05 level ( 2 tailed ) Table : T11-Arm UE correlation for stimulation (threshold & for maximum amplitude) for 1st and 2nd Day

Subjects C7 UE T11 UE T11 LE M.A 5 4 H.G 6 D.H 7 M.S 3 S.G A.A A.S M.K Mean ± SD 4.4±0.8 3.5±0.5 3.9±1.2 Table: VAS For Male Subjects For MMR Stimulation (C 7 Upper Extremity And T11 Upper And Lower Extremity)

Subjects C7 UE T11 UE T11 LE E.K 8 6 7 A.A 5 3 S.U 4 K.A R.K A.K S.A D.D F.O Mean +SD 5±1.4 4±0.9 4.4±1.3 Table: VAS for Female subjects for MMR stimulation (C7 Upper extremity and T 11 Upper and Lower Extremity)

Gender C7 - UE T11-12 -UE C7 - LE T11-12 - LE Females 5 ± 1.4 4 ± 0.9 5 ± 1.4 4 ± 0.9 4.2±1 4.4 ± 1.3 Males 4.4 ± 0.8 3.5 ± 0.5 4±0.8 3.9 ± 1.2 Table : VAS for female and male subjects during C7 and T11-12 spinal stimulation while recording upper limbs and lower limb MMR.

Right Leg Left Leg

Muscles/ Legs 1ST day Amp/ mv 2nd day VMO -R 4.2±3.7 4.3±4.1 VMO -L 3.9±3.5 3.8±3. MH -R 4.4±2.4 3.7±1.9 MH - L 3.5±1.9 3.4±1.8 SOL-R 6.7±5.3 6±3.3 SOL -L 6±3.8 5.7±3.3 TA -R 2±2 1.9±.7 TA -L 1.7±1.5 Table : T11- 12 Lower Extremity MMR amplitudes (Mean ±SD)

Table: T11 LE- MMR Amplitude Correlation (1st And 2nd Day) Muscles R- LE 1st vs. 2nd L- LE LE 1ST R vs L 2nd R vs L VMO Pearson Correlation Sig. (2-tailed) .934** .000 .893** .927** .864** MH .930** .747** .001 .900** * .723** .002 SOL .828** .858** .895** .705** .003 TA .875** .882** .861** .932** ** Correlation is significant at the 0.01 level ( 2 tailed ) *Correlation is significant at the 0.05 level ( 2 tailed ) Table: T11 LE- MMR Amplitude Correlation (1st And 2nd Day)

Table :T11 LE MMR Latencies Mean and ± SD RIGHT vs LEFT LEG 1ST day 2nd day VMO -R 9.4±2.3 9.6±2.3 VMO- L 9.5±2.1 9.4±2 M.H -R 8.3±2.6 8.4±2.6 M.H- L 8.7±2.4 SOL-R 15.5±2.6 15±3 SOL - L 15.1±2.6 15.5±2.8 T.A -R 14.3±2 14±2.2 T.A- L 14±2 Table :T11 LE MMR Latencies Mean and ± SD

Table : T11- LE MMR Latencies (1st Day and 2nd Day Correlations) Muscles R- LE 1st vs. 2nd L- LE LE 1ST R vs L 2nd R vs L VMO Pearson Correlation Sig. (2-tailed) 974** .000 .983** .987** .978** MH .977** .910** .991** .901** SOLEUS .790** .928** .865** .916** T.A .959** .834** .810** ** Correlation is significant at the 0.01 level ( 2 tailed ) *Correlation is significant at the 0.05 level ( 2 tailed ) Table : T11- LE MMR Latencies (1st Day and 2nd Day Correlations)

Stimulation current 1ST DAY 2ND DAY THR–R 60.3±12.7 59.7±11.9 THR-L 61.4±13.1 61.±12.6 MAX. AMPLITUDE-R 95.7±9.3 96.9±8 MAX. AMPLITUDE-L 96.7±8.3 Table : T11 Lower Extremity MMR Stimulation (Threshold and Maximum Amplitude) for 1st and 2nd day

Fig : T11 Lower Extremity MMR Stimulation Threshold and Maximum Current Mean ± Standard Deviations for 1st and 2nd day

Fig : T11 Lower Extremity MMR Stimulation Threshold and Maximum Current Mean ± Standard Deviations for 1st and 2nd day

VAS for MMR stimulation from,C7 and T11 Upper and T11 lower extremity Subjects C7 UE T11 UE T11 LE M.A 5 4 H.G 6 D.H 7 M.S 3 S.G A.A A.S M.K Mean ±SD 4.4±0.8 3.5±0.5 3.9±1.2 Subjects C7 UE T11 UE T11 LE E.K 8 6 7 A.A 5 3 S.U 4 K.A R.K A.K S.A S. D.D F.O Mean ±SD 5±1.4 4±0.9 4.4±1.3 Male subjects Female subjects

CONCLUSIONS These results indicate the MMR studies can be useful with patients of neurological disorders tested at serial tests. Results also indicate a similarity between right and left upper and lower limbs for possible testing comparison.

REFERENCES Sabbahi M. and Salik Y. Thoracolumbar … Sabbahi M. and Salik Y. Cervical Multisegmental

Percent of MMR amplitude of more proximal muscles to the APB (& the opposite) with T11 (left) & C7 (Right) stimulation in the right & left arms T11 APB/FCR APB/BB ABP/TB RIGHT 245.72% 348.29% 231.87% LEFT 243.16% 303.46% 191.27% C7 APB/FCR APB/BB ABP/TB RIGHT 179.49% 130.20% 72.90% LEFT 180.37% 123.54% 85.06% T11 FCR/APB BB/APB TB/APB RIGHT 74.01% 55.54% 72.30% LEFT 70.74% 73.31% 92.85% C7 FCR/APB BB/APB TB/APB RIGHT 55.71% 76.81% 72.90% LEFT 55.44% 80.95% 77.02%

Percent of MMR amplitude of more proximal muscles to the APB (& the opposite) with T11 (left) & C7 (Right) stimulation in the right & left arms C7 stimulation T11 stimulation R-APB APB/FCR FCR/APB APB/BB BB/APB APB/TB TB/APB AVERAGE 213.96% 46.74% 228.54% 43.76% 180.90% 55.28% STDEV 295.06% 33.89% 152.02% 65.78% 125.04% 79.97% R-APB AMP APB/FCR FCR/APB APB/BB BB/APB APB/TB TB/APB AVERAGE 179.49% 55.71% 130.20% 76.81% 137.17% 72.90% STDEV 201.10% 49.73% 131.63% 75.97% 117.56% 85.06% L-APB APB/FCR FCR/APB APB/BB BB/APB APB/TB TB/APB AVERAGE 180.37 55.44% 123.54% 80.95% 129.83% 77.02% STDEV 196.92% 50.78% 126.48% 79.06% 163.63% 61.11% L-APB APB/FCR FCR/APB APB/BB BB/APB APB/TB TB/APB AVERAGE 186.94% 53.49% 183.81% 54.40% 146.38% 68.31% STDEV 199.03% 50.24% 117.38% 85.20% 121.49% 82.31%

Uses of MMR studies (research & Clinical)

II. Patient’s studies: a. Our studies on Patients with SCI b II. Patient’s studies: a. Our studies on Patients with SCI b. Does the MMR signal correlate to function. c. Our studies on Patients with Radiculopathy, MS, Other pathologies. d. Previous & Other studies on patients using MMR. e.ASIA & MMR: A CLINICAL-ELECTROPHYSIOLOGICAL COMPLIMENT (DEVELOPING ELECTROPHYSIOLOGIC CLASSIFICATION OF SCI)

Our studies on Patients with SCI

Testing Spinal Cord Circutries With MMR: Is A Complete Spinal Cord Injury Complete? Mohamed A. Sabbahi; Selda Uzun; Fikriye Ovak Bittar. Texas Woman’s University, School of Physical Therapy, Houston, Texas and Texas Electrophysiology Services, Houston, Texas

C7-T11 MMR STUDIES FOR UPPER AND LOWER LIMBS ON SCI PATIENTS COMPARISON THESE RESULTS WITH SCI ASIA LEVELS.

INTRODUCTION Multi segmental motor responses (MMR ) have been recorded in the upper and lower limbs. However comparison between normal subjects and SCI patients MMR results has not been studied. Also comparison of testing these responses with ASIA results has not been reported.

The purpose of this study is to evaluate the use of MMR in testing spinal circuitries (ascending & descending pathways) in patients with SCI of different ASIA categories.

It is hypothesized that MMR testing will reveal some intact circuits that could not be tested by the clinical testing of ASIA in the so-called complete SCI

METHODS: Subjects were 12 SCI males with age range (38.5± 13.2);

9 with complete (ASIA-A), 3 with incomplete (2, ASIA-B, one ASIA-C) injuries. Levels of SCI include cervical (5 patients), thoracic (7).

The cause of injuries includes gunshot wound (6), car accident (2), falls (3), and stabbed wound (1). All subjects suffer bladder and bowel disorders.

After signing consent forms, subjects were tested with Cervical and Thoracolumbar MMR. Surface electrical stimulation (1 msec, 0.2 pps at response max) of C7 and T11-12 were carried out while recording muscular responses (4 channels) in both upper (APB,FCR,BI and TRI) and lower (VMO,MH,Sol., and TA) limbs using surface electrodes

SUBJECTS GENDER Age Height C7-T11 cm Weight SCI level DOI Months ASIA J.S M 35 178 33.5 73 C6-7 100 A S.A 54 164.6 28.5 82 C3-C7 57 A.P 21 176.8 30 63.6 C3 16 A.M 39 165.1 29.5 80.74 C4-C5 56 M.Pl 38 29 68 T4 36 J.R 176 T8 83 R.R 42 186 30.5 T9-11 103 M.G 180 27.5 91 T11-12 60 H.L.G 161.4 9 R.S 25 177 81.6 T 11 10 B J.O.H 170.7 74.5 T5-T7 3 G.G 65 31 89 C5-C6 C

J.S A 24 22 B&B disorder S.A 12 18 A.P 14 17 A.M 8 20 M.Pl 50 44 J.R SUBJECTS ASIA ASIA MOTOR SCORE ASIA PINPRICK ASIA LIGHT TOUCH Bladder/Bowel dis. J.S A 24 22 B&B disorder S.A 12 18 A.P 14 17 A.M 8 20 M.Pl 50 44 J.R 60 R.R 62 M.G 52 70 H.L.G 72 R.S B 68 J.O.H 48 G.G C

Subjects were tested with Cervical and Thoracolumbar MMR. Surface electrical stimulation (1 msec, 0.2 pps at response max) of C7 and T11-12 were carried out while recording muscular responses (4 channels) in both upper (APB,FCR,BI and TRI) and lower (VMO,MH,Sol., and TA) limbs using surface electrodes.

The peak-to-peak amplitude and deflection latency were the dependent parameters and results were analyzed using descriptive statistics.

RESULTS showed that small amplitude MMR signal was recorded in the lower limb muscles in 7 ASIA-A, one ASIA-B and one ASIA-C patients during C7 or T11-12 stimulation. This indicates that signal passes through the injury sites

Upper limb signal to T11-12 stimulation were recorded in most subjects and showed robust amplitude indicating intact ascending pathways throughout the lesion site.

Spinal Cord Trauma Paralysis • Paralysis — loss of motor function • Flaccid paralysis — severe damage to the ventral root or anterior horn cells • lower motor neurons are damaged and impulses do not reach muscles • no voluntary or involuntary control of muscles • Spastic paralysis — only upper motor neurons of the primary motor cortex are damaged • spinal neurons remain intact and muscles are stimulated irregularly • no voluntary control of muscles Transection • Cross sectioning of the spinal cord at any level results in total motor and sensory loss in regions inferior to the cut • Paraplegia — transection between T1 and L1 • Quadriplegia — transection in the cervical region http://www.profelis.org/webpages-cn/lectures/neuroanatomy_3.html

Incomplete Spinal Cord Injury Quadriplegia, incomplete %31.2 Paraplegia, complete % 28.2 Paraplegia, incomplete %23.1 Quadriplegia, complete %17.5

Types of Incomplete Spinal Injury Anterior Cord Syndrome: is when the damage is towards the front of the spinal cord, Central Cord Syndrome: is when the damage is in the centre of the spinal cord. This typically results in the loss of function in the arms, but some leg movement may be preserved. Posterior Cord Syndrome: is when the damage is towards the back of the spinal cord. This type of injury may leave the person with good muscle power, pain and temperature sensation, however they may experience difficulty in coordinating movement of their limbs. This is a type of incomplete spinal cord injury Brown-Séquard syndrome: is when damage is towards one side of the spinal cord. This results in impaired or loss of movement to the injured side, but pain and temperature sensation may be preserved. The opposite side of injury will have normal movement, but pain and temperature sensation will be impaired or lost. This is a type of incomplete spinal cord injury Cauda equina lesion: The Cauda Equina is the mass of nerves which fan out of the spinal cord at between the first and second Lumbar region of the spine. The spinal cord ends at L1 and L2 at which point a bundle of nerves travel downwards through the Lumbar and Sacral vertebrae. Injury to these nerves will cause partial or complete loss of movement and sensation. It is possible, if the nerves are not too badly damaged, for them to grow again and for the recovery of function. This is a type of incomplete spinal cord injury ( Ref: Spinal Injury Network )

Central Cord Syndrome Anterior Cord Syndrome Brown Séquard Syndrome Incomplete Spinal Cord Injuries

C7 UPPER EXTREMITY MMR AMPLITUDES, RIGHT-LEFT COMPARISON TRICEPS C7 UPPER EXTREMITY MMR AMPLITUDES, RIGHT-LEFT COMPARISON  SUBJECTS  SCI level  ASIA APB-R APB-L FCR-R FCR-L BI-R BI-L TRI-R TRI-L J.S C6-7 A 10.1 9.3 13 6.6 6.7 20.5 5 S.A C3-C7 4.7 1.7 1.8 2.9 1.1 5.3 2.6 A.P C3 5.1 7.4 0.6 0.8 A.M C4-C5 0.2 0.06 0.7 0.3 0.05 M.Pl T4 1.5 0.9 3.4 3.3 2.2 3.7 2.4 3 J.R T8 15.8 16 15.9 9.4 15.2 3.8 R.R T9-11 2.5 5.9 6.4 15.3 4.5 M.G T11-12 1 0.4 1.3 H.L.G 3.5 2.8 R.S T 11 B 17.8 14.5 6.2 7.6 6.5 J.O.H T5-T7 1.2 G.G C5-C6 C 4.6 8.8 3.9

A SAMPLE OF SCI PATIENT T11 UPPER LIMBS MMR. J.S , C6-C7 SCI ,ASIA A RIGHT UE LEFT UE APB FCR BI TRI

T 11 UPPER EXTREMITY MMR AMPLITUDES, RIGHT-LEFT COMPARISON APB FCR BICEPS TRICEPS T 11 UPPER EXTREMITY MMR AMPLITUDES, RIGHT-LEFT COMPARISON  SUBJECTS  SCI level  ASIA APB-R APB-L FCR-R FCR-L BI-R BI-L TRI-R TRI-L J.S C6-7 A 2.5 6.6 1.5 4 1.8 7 7.9 8.7 S.A C3-C7 4.5 1.4 2.8 2 2.7 3.6 14.2 2.9 A.P C3 19.5 7.8 2.3 1.7 0.7 0.9 A.M C4-C5 2.6 1.3 0.8 1.2 0.07 0.02 0.06 0.04 M.Pl T4 14.1 13 7.4 7.5 5.8 6.5 J.R T8 13.1 11.5 4.4 2.1 10 4.3 R.R T9-11 12.4 7.2 8.8 11 11.8 5.1 M.G T11-12 0.6 1.1 0.4 1 0.3 H.L.G 20.5 21.5 4.7 3.8 R.S T 11 B 12 10.4 5.6 5.2 6.2 5.7 J.O.H T5-T7 6.3 3.2 G.G C5-C6 C 1.9 3 0.2 0.1

Small amplitude MMR signal was recorded in the lower limb muscles in 7 ASIA-A, one ASIA-B and one ASIA-C patients during C7 or T11-12 stimulation

SCI PATIENTS C7 LOWER LIMBS MMR AMPLITUDES VMO M.H SOLEUS T.ANTERIOR SCI PATIENTS C7 LOWER LIMBS MMR AMPLITUDES  SUBJECTS  SCI level  ASIA VMO-R VMO-L M.H-R M.H-L SOL-R SOL -L TA-R TA-L J.S C6-7 A 0.3 0.2 0.1 0.01 N/A S.A C3-C7 0.4 0.08 0.05 0.03 0.07 A.P C3 0.5 A.M C4-C5 0.8 M.Pl T4 1.5 1 J.R T8 0.7 0.02 R.R T9-11 M.G T11-12 NR H.L.G R.S T 11 B J.O.H T5-T7 0.09 G.G C5-C6 C 0.06 0.04

A SAMPLE OF SCI PATIENT C7 LOWER LIMBS MMR , R.R T9-T11 , ASIA A SCI RIGHT LE LEFT LE VMO M.H SOL T.A

R.R, T9-11 ASIA A SCI. C7 RIGHT LEG MMR , COMPARING WITH NORMAL SUBJECT VMO M.H SOL T.A

SCI PATIENTS t11 LOWER LIMBS MMR AMPLITUDES VMO M.H SOLEUS T.ANTERIOR SCI PATIENTS t11 LOWER LIMBS MMR AMPLITUDES  SUBJECTS  SCI level  ASIA VMO-R VMO-L M.H-R M.H-L SOL-R SOL -L TA-R TA-L J.S C6-7 A 0.1 0.2 0.9 0.06 S.A C3-C7 0.6 0.09 A.P C3 0.4 0.3 A.M C4-C5 1.3 0.5 0.08 M.Pl T4 2 5.5 1.4 1.2 1.1 J.R T8 11.1 8.2 2.9 R.R T9-11 0.05 0.07 M.G T11-12 NR 0.02 H.L.G R.S T 11 B J.O.H T5-T7 0.7 2.5 0.8 135 G.G C5-C6 C 0.04

A SAMPLE OF SCI PATIENT T11 LOWER LIMBS MMR IN LYING POSITION , J A SAMPLE OF SCI PATIENT T11 LOWER LIMBS MMR IN LYING POSITION , J.R, T 8, ASIA A RIGHT LEG LEFT LEG VMO M.H SOL TA

A SAMPLE OF SCI PATIENT T11 LOWER LIMBS MMR IN SITTING POSITION , J A SAMPLE OF SCI PATIENT T11 LOWER LIMBS MMR IN SITTING POSITION , J.R, T 8, ASIA A RIGHT LEG LEFT LEG VMO M.H SOL TA

No such traveling signal was recorded in the other 2 ASIA-A and one ASIA-B patients for Lower Limbs from C7 and T11 stimulation.

SUBJECTS GENDER Age Height C7-T11 cm Weight SCI level DOI Months ASIA M.G M 54 180 27.5 91 T11-12 60 A H.L.G 30 161.4 68 9 R.S 25 177 29.5 81.6 T 11 10 B

C7 LEG MMR EXAMLES WITH MINIMAL RESPONSE ON THE RIGHT LIMB AND NO RESPONSE ON THE LEFT LIMB ,M.G ,T11-12 SCI,ASIA –A RIGHT LEG LEFT LEG VMO M.H SOL TA

H.L.G. T11-12 ,ASIA –A SCI,C7 RIGHT LEG MMR COMPARISON WITH NORMAL SUBJECT VMO M.H SOL TA

C7 RIGHT LEG SITTING MMR H.L.G. T11-12 ,ASIA –A SCI Normal Subject H.L.O, ASIA –A SCI, CMMR LEG NO RESPONSE,COMPARING WITH NORMAL SUBJECT

But Upper limb signal to T11-12 stimulation were recorded in these three subjects and showed robust amplitude indicating intact ascending pathways throughout the lesion site.

T11 UE MMR EXAMPLES WITH NO RESPONSE FOR LOWER LIMB BUT THERE IS SIGNALS FOR UPPER LIMB ,M.G ,T11-12 SCI,ASIA –A RIGHT UE LEFT UE APB FCR BI TRI

ASIA-C patient showed varying but larger amplitude of ascending (to UE) but lower amplitudes in descending (to LE,) signal.

C7 UE MMR . G.G, C5-6 ,ASIA-C SCI RIGHT UE LEFT UE APB FCR BI TRI

T11 UE MMR . G.G, C5-6 ,ASIA-C SCI RIGHT UE LEFT UE APB FCR BI TRI

C7 LE MMR . G.G, C5-6 ,ASIA-C SCI RIGHT LE LEFT LE VMO M.H SOL T.A

T11 LE MMR . G.G, C5-6 ,ASIA-C SCI RIGHT LE LEFT LE VMO M.H SOL T.A

Signal amplitude varies between proximal and distal limb muscles and right versus left limbs with different patients and was dependent on the extent of the injury indicating selective axonal damage in the pathways.T11-12 stimulation, below the level of the injury, resulted in small amplitude MMR signal in all muscles of the lower limbs in all SCI patients.

These results indicate that certain ascending and descending spinal pathways are still conducting viable signal through the injury sites, in most patients, and could offer hopes for some regeneration with focused rehabilitation. It also showed that ASIA classification might not reflect circuitry functions in SCI and need to be supplemented with MMR studies.

Does the MMR signal correlate to function?

ASIA & MMR: A CLINICAL-ELECTROPHYSIOLOGICAL COMPLIMENT (DEVELOPING ELECTROPHYSIOLOGIC CLASSIFICATION OF SCI)

Radiculopathy

MS & Other pathologies

Previous & Other studies on patients using MMR.

CONCLUDING REMARKS