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| Year : 1999 | Volume
: 47
| Issue : 3 | Page : 229-33 |
A study of transcranial magnetic stimulation in older (>3 years) patients of malnutrition.
Karak B, Misra S, Garg RK, Katiyar GP
Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Correspondence Address:
Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Transcranial magnetic stimulation was performed in 40 subjects. Twenty patients in the age group of 3 to 8 years and having different grades of malnutrition were included in the 'study group' whereas 20 normal children having no complaints comprised the 'control group'. The coil of the magnetic stimulator was applied tangentially over the vertex to stimulate the cortex. The motor evoked potential (MEP) was obtained using root stimulation by applying the coil at the cervical and lumbosacral spines. Recordings were made from the abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) muscles of both sides. Cortical threshold, latency and amplitude of motor evoked potential and central conduction time were recorded. Malnourished children showed significantly increased cortical threshold, prolonged cortical latency and central conduction time and reduction in amplitude of MEP. Observed delay in central motor conduction in malnourished children suggests asymptomatic involvement of corticospinal pathways.
How to cite this article:
Karak B, Misra S, Garg R K, Katiyar G P. A study of transcranial magnetic stimulation in older (>3 years) patients of malnutrition. Neurol India 1999;47:229 |
Transcranial magnetic stimulation is a safe, noninvasive and well tolerated technique for assessment of the central descending tracts of the motor system.[1] It offers a method for studying the functional maturation of corticospinal pathway and higher nervous activity. Magnetic stimulation of the motor cortex introduced by Barker et al[1] is now an established method in clinical neurophysiology. Its diagnostic value in adults has been shown in multiple sclerosis,[2] degenerative ataxic disorders,[3] strokes[4],[5] as well as in several other neurological diseases.
Koh and Eyre[6] and Eyre et al[7] had for the first time studied normal infants and children and showed that motor evoked potential could be obtained from the muscles of premature infants as early as 34 weeks. Children with spastic hemiplegia (without or with radiological evidence of brain damage), seizures, intellectual retardation and Rett's syndrome have been studied by transcranial magnetic stimulation.[8],[9] Previous studies in animals and humans have shown significant adverse effects of malnutrition on the structure and function of the brain.[10],[11] We evaluated central motor conduction in malnourished children of greater than 3 years by transcranial magnetic stimulation as our preliminary study in predominantly younger children suggested involvement of growing corticospinal tract as a result of malnutrition. Children of >3 years of age were studied because by then the process of myelination of neurons is complete and central conduction time remains relatively constant afterwards.[8]
20 patients in the age group of 3 to 8 years and having different grades of malnutrition served as study group while 20 children who were within normal range of weight for their age were included as healthy control. The parents gave their informed consent in all the patients and controls. Detailed neurological and systemic examination was performed. Children were excluded if they had following factors, 1) Presenting complaints suggesting any chronic systemic illness, particularly pointing to the involvement of nervous system; 2) past history suggestive of any neurological insult; 3) positive antenatal history and perinatal events like birth asphyxia, 4) delay in developmental milestones not attributable to malnutrition alone; 5) neurocutaneous marker and other minor or major congenital anomalies. Body weight was used to grade the severity of malnutrition as recommended by the Nutrition Sub-Committee of the Indian Academy of Pediatrics.[13] Weight of each child was taken on a spring balance (which measures upto 0.5 kg differences) with minimum clothing on the body. Weight of the 50th Harvard centile was taken and each child's weight was compared with the standard expressed as a percentage and grading of malnutrition was done as follows; - control - > 80% of standard, mildly malnourished - 61-80% of standard, and severely malnourished - < 60% of standard.
For the purpose of this study, transcranial magnetic stimulation was carried out in the electrophysiology laboratory of Division of Neurology, Institute of Medical Sciences, Banaras Hindu University. All electrophysiological investigations were carried out on Neuromatic 2000 : 2 channel digital EMG system linked with magnetic stimulator MAF-2 from Dantec Electronik, Denmark. A large circular magnetic coil with an outer diameter of 14cm was used for transcranial stimulation to evoke muscle action potential. To activate upper limb muscles, the `sweet point' of the coil was placed tangentially on the vertex, corresponding to Cz of international 10-20 system of placement of electrodes for electroencephalography. To stimulate the left cortex, side `A' was used while side `B' was used to stimulate the right cortex. To obtain the lower limb muscle evoked potential the suggested point of stimulation (7 cm anterior and 2-4 cm lateral to Cz did not hold true for our patients and several attempts (usually 3 to 4) were needed to evoke muscle action potential by frequently repositioning the coil position on the vertex. Recordings were taken from the abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) muscles bilaterally using surface electrodes. Initially, the muscle was kept relaxed. All the children needed a facilitation process, which consisted of voluntary contraction of the muscle to a moderate degree, or passive contraction in younger children, again to a moderate degree, to induce the MEP. Magnetic stimuli were also applied over the cervical spine and lumbo-sacral spine respectively for measuring peripheral conduction time (root latency) for upper and lower limb muscles and calculating central motor conduction time (CCT). This was easier in subjects requiring less stimulus. The latency from cortical stimulation to the onset of the MEP was recorded as the cortical latency, whereas the latency from root stimulation to the onset of the MEP was recorded as the root latency. Central motor conduction time (CCT) was calculated by `CL minus RL' using MEP following transcranial and spinal magnetic stimulation. The cortical threshold was defined as the percentage of maximum output of stimulus intensity (1500 tesla units) required to induce an evoked response of >20mv in amplitude.
Following parameters were recorded - i) cortical threshold, ii) latency of MEP, iii) amplitude of MEP and iv) central conduction time. These parameters were evaluated in both study and control group children. APB muscles in upper limbs and EDB muscles in lower limbs were used to induce cortical threshold on both sides of the body. These parameters were compared between left and right side, study and control group and impact of severity of malnutrition was assessed statistically by unpaired `t' test.
Demographic characteristics of study and control group are provided in [Table I] [Table II] shows that higher cortical threshold was required in both APB and EDB muscles in both sides and in both malnourished and control group. The malnourished children required a significantly higher stimulation threshold as compared to control on both sides. Milder degree of malnutrition had no significant impact on the threshold, but the severe degree of malnutrition required a significantly higher cortical threshold to induce MEP. [Table III] showed statistically significant prolongation of cortical latency, central conduction time and reduction in amplitude of MEPs in patients of malnutrition in APB muscle and also statistically significant prolongation of CCT in EDB muscle as compared to control group. No significant difference was observed in MEP parameters between left and right side of APB and EDB muscle. [Table IV] shows a prolonged cortical latency and central conduction time in both milder and severe degree of malnutrition compared with control group, however, these differences were found to be statistically significantly only for APB muscles.
Magnetic stimulation is an excellent method for studying the functional maturation of the corticospinal pathway. Conduction time in the corticospinal pathway falls rapidly in first 2 years of life and then remains approximately constant. The initial fall in the central motor conduction time can be accounted for by the process of myelination which is almost complete during the first 2 years. The relative constancy in central motor conduction time thereafter implies a gradual increase in conduction as the child grows older. It has also been established that the conduction velocities in peripheral motor nerves reach adult values by 3 years of age. Histochemical studies of necropsy samples also suggest that myelination of the corticospinal tract is complete by 3 years of age. To avoid the effect of age related changes of the maturation on nervous system, we included only children who were above 3 years of age so that acquired effect of malnutrition on growing nervous system could be established.[6],[7]
In the past, the techniques of transcranial magnetic stimulation have been tried in various childhood afflictions of nervous system. Spastic hemiplegia in childhood with no intellectual or other deficits was thought to be due to corticospinal tract lesions. A study of 11 children showed normal responses to magnetic stimulation from unaffected side, but delayed or absent responses from the plegic side. Muller et al[8] showed motor evoked potential abnormalities in 13 out of 20 patients, 7 of whom had a corresponding corticospinal tract lesions on MRI. Four of the remaining 7 patients with normal motor evoked potentials had MRI lesions, apparently affecting the corticospinal tracts. Transcranial magnetic stimulation of children with spastic quadriplegia with evidence of brain damage, seizures and intellectual retardation gave normal responses bilaterally, suggesting that lesion was higner in the corticospinal tracts. Rett's syndrome, a neurodegenerative condition affecting girls, appears after normal initial development in the first year and manifests by loss of motor skills, manipulation, locomotion, speech and eventual paucity of voluntary movement. Magnetic stimulation showed low thresholds for corticospinal activation with long duration responses. Responses could be obtained in the absence of facilitation and had a shorter latency than normal. Physiologically this suggests a `supereffective' corticospinal pathway perhaps due to increase excitability of corticospinal neurons or denser synaptic connections on the anterior horn cells.[14] The effects of undernutrition on the immature nervous system has been the subject of intensive investigations. Neuropathological studies have revealed that brain of a malnourished infant was small for the infant's chronological age, and the number of neurons, degree of myelination, and total cerebral lipid content was reduced. Chopra et al,[15] reported significantly delayed nerve conduction times in both the marasmic and the kwashiorkor forms of malnutrition even in the absence of overt associated vitamin deficiency. About half of patients with the more severe forms of protein energy malnutrition have segmental demyelination. In case of severe and long lasting malnutrition, arrested myelination with a persistence of the small myelinated fibres is seen. However, in the present series we could not observe any difference in root latencies indicative of peripheral conduction. In this study we tried to establish the effect of malnutrition on growing but myelinated corticospinal tracts. We easily obtained MEPs in children of both study and control group; however, facilitation was required in all the children and this has been attributed to a lower cervical excitability than adults due to neuronal immaturity. The malnourished children have a significantly increased cortical threshold to induce MEP, prolonged cortical latencies and central conduction time. This prolongation of CCT is a sensitive indicator of abnormality in descending motor pathway. Increased cortical threshold represents dysfunction of maturation process of the cortex as result of malnutrition. The relationship of maturation process of the cortex had been studied in experimental primates, but data in humans is scantly.[6],[16] We observed a significant difference in cortical stimulation threshold and central motor conduction between patients of malnutrition and controls. Higher cortical threshold indicates asymptomatic pyramidal involvement in these patients. Being a case-control study we did not evaluate the prospective changes in various parameters of central motor conduction following treatment of malnutrition. Malnutrition is likely to affect further growth of myelinated corticospinal tract fibers.
Past clinical and histopathological studies in malnourished children suggested that neurological involvement was either cortical in the form of altered cognitive parameters, or of peripheral nerves. Abnormal central motor conduction parameters in our study suggest adverse effect of malnutrition on growth of fully myelinated pyramidal or corticospinal tracts.
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