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Rapid magnetic stimulation with sonolysis for gait apraxia due to normal pressure hydrocephalus and cerebral ischemia
International Congress Series 1300 (2007) 341 – 344
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Rapid magnetic stimulation with sonolysis for gait apraxia due to normal pressure hydrocephalus and cerebral ischemia G. Devathasan ⁎, D. Dinesh Mt. Elizabeth Hospital, Division of Neurology, No. 11-16 Mt. Elizabeth Medical Centre, 3 Mt. Elizabeth Road, 228510, Singapore
Abstract. Results of shunting or other treatment for gait apraxia associated with normal pressure hydrocephalus and periventricular ischemia are still dubious and the condition is progressive. We treated 15 consecutive cases by a two pronged approach using rapid magnetic stimulation (RMS) and sonolysis. Patients selected presented primarily with gait apraxia. All were evaluated by full clinical and blood examination, MRI, MRA and ultrasound of the neck and cerebral vessels. Rapid magnetic stimulation was administered daily for seven days and sonolysis or therapeutic ultrasound for three days. Patients were reviewed for three months and therapy repeated. The Barthel's index was used for evaluation. The data before treatment was compared with that after six months and there was overall statistically significant improvement. Shunt therapy could be avoided and two post shunt failures responded to this regime. © 2007 Elsevier B.V. All rights reserved. Keywords: Normal pressure hydrocephalus; Cerebral ischemia; Gait apraxia; Magnetic gait; Shunt failure; Rapid magnetic stimulation (RMS); Sonolysis; Therapeutic ultrasound
1. Introduction Gait apraxia or magnetic gait usually affects the elderly and is a distressing, progressive condition. It is due either to normal pressure hydrocephalus or in combination with diffuse cerebral and periventricular ischemia. Diagnosis is established by MRI, which shows dilated ventricles in the absence of mass lesions or obstruction to CSF flow. There is often associated periventricular infiltrate, diffuse white ischemic spots in the white matter and ⁎ Corresponding author. Tel.: +65 697304401; fax: +65 62357637. E-mail address: [email protected] (G. Devathasan). 0531-5131/ © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2007.02.042
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G. Devathasan, D. Dinesh / International Congress Series 1300 (2007) 341–344
slight atrophy [1,2]. The atrophy if present is out of proportion to the ventricular dilatation. Power in the limbs remains intact but execution of gait is impaired and the stride becomes progressively smaller and unsteady. The lesser symptoms include imbalance, poor bladder control, and slight decline in cognition. CSF manometric studies show varying pressure and ventricular peritoneal shunting until now is the treatment tried. The effectiveness of CSF shunting has never been demonstrated convincingly [3]. Practically all cases if left untreated progress to immobility and significant cognition impairment. Based on our preliminary pilot studies, we further investigated 15 consecutive cases and treated them by a novel two pronged approach, which is by using rapid magnetic stimulation and therapeutic ultrasound or sonolysis. 2. Patients and methods 2.1. Patients The patients selected consecutively had gait apraxia as the main symptom. Minor symptoms included poor bladder control and imbalance. All had full clinical and biochemical evaluation with MRI, MRA, 3D duplex color-coded ultrasound of neck and cerebral vessels, and echocardiogram. Patients excluded were those with significant paralysis, large infarcts, seizures, subdural bleed, spondylotic myelopathy, dementia, and any other causes that would easily explain the gait difficulty. The patients were scored according to the Barthel's index of activities for daily living, using ten criteria with a total maximum favorable score of 20 and minimal adverse score of 0. The criteria include bowel status, bladder status, grooming, toilet use, feeding, transfer, mobility, dressing, stairs, and bathing. Patients were routinely evaluated pre and post treatment, and at three monthly intervals. The therapy described below was repeated during follow-ups (Table 1). Table 1 Barthel's total score for each patient 10 parameters each score from 0 to 1, 2 or 3. Max 20 Patient
Before treatment
Six month after
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
13 13 14 14 12 16 6 7 12 14 10 11 13 16 10
20 18 19 19 18 18 6 12 8 15 17 20 19 20 15
p-value 0.004 2 sample t test.
G. Devathasan, D. Dinesh / International Congress Series 1300 (2007) 341–344
343
2.2. Methods of therapy Rapid magnetic stimulation was administered daily for seven days just below motor and pain threshold between 45 to 55 a/us, totaling 1000 pulses daily, delivered at 15 Hz with 15 s interval. Sites stimulated were over the skull vault i.e. frontal, parietal, and occipital, either side and near the midline. The large 90 mm coil was moved in slow motion and at least 200 pulses were delivered just anterior to the motor cortex for each patient. Standard safety precautions were followed [4]. Sonolysis or ultrasound therapy [5–8] was applied for three consecutive days, for 15 min daily using simultaneously two 1 MHz probe powered at 0.3 w/sq cm for the stationary probe and between 0.7 w/sq cm to 1.2 w/sq cm for another hand held and rapidly moving probe. The second moving probe delivered more power. Pain was a limiting and safety factor. Four skull windows were used to access the cerebral circulation i.e. two temporal and two sup-occipital sites. The findings of the MRA and diagnostic ultrasound of the vessels determined the positions of the probes. 3. Results The table shows overall statistically significant improvement for this progressive illness at the six-month interval. Two patients recruited were post shunt failures and previously continued to deteriorate after the ventricular peritoneal shunts. Both showed good response to this treatment and remained mobile. Three patients were offered shunt treatment elsewhere but turned down the procedure. These three responded satisfactorily. Another three were mildly apraxic and showed dramatic sustained improvement soon after initiation of therapy. Two patients also presented with the syndrome of inappropriate serum antidiuretic hormone (SIADH) and had the low sodium corrected first. In addition to improvement of gait, the syndrome resolved and the patients did not require fluid restriction, which is the standard known treatment. Three patients were non-responders. All three were rather advanced in their illness with significant cognition decline. They remained wheelchair bound and severely apraxic. 4. Discussion The data indicate that rapid magnetic stimulation appears to give quick response to patients with magnetic gait apraxia as defined above [see ref. [1]]. We believe that it acts by activating cortical ischemic areas especially at the medially located higher gait execution centre and micturation centre anterior to the motor strip. Both areas are closely located. We noted that when the gait improved the bladder symptoms also ameliorated. We have not routinely repeated the MRI yet to seen whether ventricular sizes shrink, as this would have required quantitative evaluation prior to recruitment and a separate study. RMS therapy appears to help re-absorption of CSF via the arachnoid villi. The villi are richly innervated by sympathetic fibers running through the 5th, 7th, and 11th cranial nerves and for this reason we kept the stimulating coil near the midline. In addition, pain is less when the coil is kept near the midline. With the 90 mm coil, stimulation depth is up to 5 cm and this would easily reach cortical structures. The
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G. Devathasan, D. Dinesh / International Congress Series 1300 (2007) 341–344
responses in general are not sustained over the weeks and we had therefore incorporated sonolysis. Sonolysis or therapeutic ultrasound is now an increasingly evaluated therapy for stroke treatment. We had modified the methodology to make it more practical and we used a standard low cost therapeutic ultrasound machine. In essence, we delivered the same total power per patient as in the CLOTBUST and other studies [5,7], but with greater intensity and shorter duration and found no adverse effects to date. Therapeutic ultrasound helps to sustain the response, which patients receive with rapid magnetic stimulation. It improves the microcirculation and cerebral autoregulation [6]. In addition, micro-clots are probably dissolved by cavitation and spinning of red cells. We have now extended the therapy to other apraxic patients and noted similar results. This simple innovative combined therapy appears to be an effective, safe, and low cost way to treat this progressive condition, which afflicts many elderly subjects. It is worthwhile to design a double blind study, and investigate each therapeutic modality separately. References [1] G.D. Silverberg, Normal pressure hydrocephalus (NPH): ischaemia, CSF stagnation or both, Brain 127 (2004) 947–948. [2] S. Hakim, R.D. Adam, The special clinical problem of symptomatic hydrocephalus with normal cerebral spinal fluid pressure. Observations on CSF dynamics, J. Neurol. Sci. 2 (1965) 307–327. [3] J. Vannesto, Shunting normal pressure hydrocephalus; do the benefits outweigh the risks, Neurology 42 (1992) 54–59. [4] A. Pascual-Leone, et al., Safety of rapid-rate transcranial magnetic stimulation in normal volunteers, Electroencephalogr. Clin. Neurophysiol. 89 (1993) 120–130. [5] J. Eggers, et al., Sonothrombolysis in acute ischemic stroke for patients ineligible for rt-PA, Neurology 64 (2005) 1052–1054. [6] A.V. Alexandrov, C.A., et al., Ultrasound improves tissue perfusion through a nitric oxide dependent mechanism, Thromb. Haemost. 88 (2002) 865–870. [7] P.D. Syme, The use of Transcranial Doppler ultrasonography as a “cerebral stethoscope” for the assessment and treatment of acute stroke, J. R. Coll. Physicians Edinb. 36 (2005) 17–28. [8] M.A. Sloan, et al., Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcom. of the American Academy of Neurology, Neurology 62 (2004) 1468–1481.
www.ics-elsevier.com
Rapid magnetic stimulation with sonolysis for gait apraxia due to normal pressure hydrocephalus and cerebral ischemia G. Devathasan ⁎, D. Dinesh Mt. Elizabeth Hospital, Division of Neurology, No. 11-16 Mt. Elizabeth Medical Centre, 3 Mt. Elizabeth Road, 228510, Singapore
Abstract. Results of shunting or other treatment for gait apraxia associated with normal pressure hydrocephalus and periventricular ischemia are still dubious and the condition is progressive. We treated 15 consecutive cases by a two pronged approach using rapid magnetic stimulation (RMS) and sonolysis. Patients selected presented primarily with gait apraxia. All were evaluated by full clinical and blood examination, MRI, MRA and ultrasound of the neck and cerebral vessels. Rapid magnetic stimulation was administered daily for seven days and sonolysis or therapeutic ultrasound for three days. Patients were reviewed for three months and therapy repeated. The Barthel's index was used for evaluation. The data before treatment was compared with that after six months and there was overall statistically significant improvement. Shunt therapy could be avoided and two post shunt failures responded to this regime. © 2007 Elsevier B.V. All rights reserved. Keywords: Normal pressure hydrocephalus; Cerebral ischemia; Gait apraxia; Magnetic gait; Shunt failure; Rapid magnetic stimulation (RMS); Sonolysis; Therapeutic ultrasound
1. Introduction Gait apraxia or magnetic gait usually affects the elderly and is a distressing, progressive condition. It is due either to normal pressure hydrocephalus or in combination with diffuse cerebral and periventricular ischemia. Diagnosis is established by MRI, which shows dilated ventricles in the absence of mass lesions or obstruction to CSF flow. There is often associated periventricular infiltrate, diffuse white ischemic spots in the white matter and ⁎ Corresponding author. Tel.: +65 697304401; fax: +65 62357637. E-mail address: [email protected] (G. Devathasan). 0531-5131/ © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2007.02.042
342
G. Devathasan, D. Dinesh / International Congress Series 1300 (2007) 341–344
slight atrophy [1,2]. The atrophy if present is out of proportion to the ventricular dilatation. Power in the limbs remains intact but execution of gait is impaired and the stride becomes progressively smaller and unsteady. The lesser symptoms include imbalance, poor bladder control, and slight decline in cognition. CSF manometric studies show varying pressure and ventricular peritoneal shunting until now is the treatment tried. The effectiveness of CSF shunting has never been demonstrated convincingly [3]. Practically all cases if left untreated progress to immobility and significant cognition impairment. Based on our preliminary pilot studies, we further investigated 15 consecutive cases and treated them by a novel two pronged approach, which is by using rapid magnetic stimulation and therapeutic ultrasound or sonolysis. 2. Patients and methods 2.1. Patients The patients selected consecutively had gait apraxia as the main symptom. Minor symptoms included poor bladder control and imbalance. All had full clinical and biochemical evaluation with MRI, MRA, 3D duplex color-coded ultrasound of neck and cerebral vessels, and echocardiogram. Patients excluded were those with significant paralysis, large infarcts, seizures, subdural bleed, spondylotic myelopathy, dementia, and any other causes that would easily explain the gait difficulty. The patients were scored according to the Barthel's index of activities for daily living, using ten criteria with a total maximum favorable score of 20 and minimal adverse score of 0. The criteria include bowel status, bladder status, grooming, toilet use, feeding, transfer, mobility, dressing, stairs, and bathing. Patients were routinely evaluated pre and post treatment, and at three monthly intervals. The therapy described below was repeated during follow-ups (Table 1). Table 1 Barthel's total score for each patient 10 parameters each score from 0 to 1, 2 or 3. Max 20 Patient
Before treatment
Six month after
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
13 13 14 14 12 16 6 7 12 14 10 11 13 16 10
20 18 19 19 18 18 6 12 8 15 17 20 19 20 15
p-value 0.004 2 sample t test.
G. Devathasan, D. Dinesh / International Congress Series 1300 (2007) 341–344
343
2.2. Methods of therapy Rapid magnetic stimulation was administered daily for seven days just below motor and pain threshold between 45 to 55 a/us, totaling 1000 pulses daily, delivered at 15 Hz with 15 s interval. Sites stimulated were over the skull vault i.e. frontal, parietal, and occipital, either side and near the midline. The large 90 mm coil was moved in slow motion and at least 200 pulses were delivered just anterior to the motor cortex for each patient. Standard safety precautions were followed [4]. Sonolysis or ultrasound therapy [5–8] was applied for three consecutive days, for 15 min daily using simultaneously two 1 MHz probe powered at 0.3 w/sq cm for the stationary probe and between 0.7 w/sq cm to 1.2 w/sq cm for another hand held and rapidly moving probe. The second moving probe delivered more power. Pain was a limiting and safety factor. Four skull windows were used to access the cerebral circulation i.e. two temporal and two sup-occipital sites. The findings of the MRA and diagnostic ultrasound of the vessels determined the positions of the probes. 3. Results The table shows overall statistically significant improvement for this progressive illness at the six-month interval. Two patients recruited were post shunt failures and previously continued to deteriorate after the ventricular peritoneal shunts. Both showed good response to this treatment and remained mobile. Three patients were offered shunt treatment elsewhere but turned down the procedure. These three responded satisfactorily. Another three were mildly apraxic and showed dramatic sustained improvement soon after initiation of therapy. Two patients also presented with the syndrome of inappropriate serum antidiuretic hormone (SIADH) and had the low sodium corrected first. In addition to improvement of gait, the syndrome resolved and the patients did not require fluid restriction, which is the standard known treatment. Three patients were non-responders. All three were rather advanced in their illness with significant cognition decline. They remained wheelchair bound and severely apraxic. 4. Discussion The data indicate that rapid magnetic stimulation appears to give quick response to patients with magnetic gait apraxia as defined above [see ref. [1]]. We believe that it acts by activating cortical ischemic areas especially at the medially located higher gait execution centre and micturation centre anterior to the motor strip. Both areas are closely located. We noted that when the gait improved the bladder symptoms also ameliorated. We have not routinely repeated the MRI yet to seen whether ventricular sizes shrink, as this would have required quantitative evaluation prior to recruitment and a separate study. RMS therapy appears to help re-absorption of CSF via the arachnoid villi. The villi are richly innervated by sympathetic fibers running through the 5th, 7th, and 11th cranial nerves and for this reason we kept the stimulating coil near the midline. In addition, pain is less when the coil is kept near the midline. With the 90 mm coil, stimulation depth is up to 5 cm and this would easily reach cortical structures. The
344
G. Devathasan, D. Dinesh / International Congress Series 1300 (2007) 341–344
responses in general are not sustained over the weeks and we had therefore incorporated sonolysis. Sonolysis or therapeutic ultrasound is now an increasingly evaluated therapy for stroke treatment. We had modified the methodology to make it more practical and we used a standard low cost therapeutic ultrasound machine. In essence, we delivered the same total power per patient as in the CLOTBUST and other studies [5,7], but with greater intensity and shorter duration and found no adverse effects to date. Therapeutic ultrasound helps to sustain the response, which patients receive with rapid magnetic stimulation. It improves the microcirculation and cerebral autoregulation [6]. In addition, micro-clots are probably dissolved by cavitation and spinning of red cells. We have now extended the therapy to other apraxic patients and noted similar results. This simple innovative combined therapy appears to be an effective, safe, and low cost way to treat this progressive condition, which afflicts many elderly subjects. It is worthwhile to design a double blind study, and investigate each therapeutic modality separately. References [1] G.D. Silverberg, Normal pressure hydrocephalus (NPH): ischaemia, CSF stagnation or both, Brain 127 (2004) 947–948. [2] S. Hakim, R.D. Adam, The special clinical problem of symptomatic hydrocephalus with normal cerebral spinal fluid pressure. Observations on CSF dynamics, J. Neurol. Sci. 2 (1965) 307–327. [3] J. Vannesto, Shunting normal pressure hydrocephalus; do the benefits outweigh the risks, Neurology 42 (1992) 54–59. [4] A. Pascual-Leone, et al., Safety of rapid-rate transcranial magnetic stimulation in normal volunteers, Electroencephalogr. Clin. Neurophysiol. 89 (1993) 120–130. [5] J. Eggers, et al., Sonothrombolysis in acute ischemic stroke for patients ineligible for rt-PA, Neurology 64 (2005) 1052–1054. [6] A.V. Alexandrov, C.A., et al., Ultrasound improves tissue perfusion through a nitric oxide dependent mechanism, Thromb. Haemost. 88 (2002) 865–870. [7] P.D. Syme, The use of Transcranial Doppler ultrasonography as a “cerebral stethoscope” for the assessment and treatment of acute stroke, J. R. Coll. Physicians Edinb. 36 (2005) 17–28. [8] M.A. Sloan, et al., Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcom. of the American Academy of Neurology, Neurology 62 (2004) 1468–1481.