Name: utility of dissociated intrinsic hand muscle atrophy in the diagnosis of amyotrophic lateral sclerosis
Uploaded: 2014-03-04T14:00:00
Description: Watch this Scientific Journal Video about Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis at JoVE.com

Funding support from the Motor Neuron Disease Research Institute of Australia (MNDRIA), Sylvia and Charles Viertel Charitable Foundation Clinical Investigator grant, Ramaciotti Foundation and National Health and Medical Research Council of Australia (Project grant number APP1024915)&#160;is gratefully acknowledged.&#160;

1. Patient Preparation
<ol>
	<li>Recruit patients prospectively and consecutively. Note: The following protocol is approved by the Sydney West Area Health Service Human Research Ethics Committees. Informed consent was provided by all patients. Patients were recruited prospectively and consecutively from the ALS/neuromuscular clinic at Westmead Hospital.</li>
	<li>Determine suitability of ALS patients for testing. Exclude patients who are not diagnosed with ALS or a neuromuscular disorder.</li>
	<li>Exclude patients wit...

<ol>
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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+&#8220;split+hand+syndrome&#8220;.">The &#8220;split hand syndrome&#8220;.</a> Muscle Nerve. 23, 138 (2000).</li><li>Kuwabara, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dissociated+small+hand+muscle+atrophy+in+amyotrophic+lateral+sclerosis:+frequency,+extent,+and+specificity.">Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity.</a> Muscle Nerve. 37, 426-430 (2008).</li><li>Kuwabara, S., Mizobuchi, K., Ogawara, K., Hattori, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dissociated+small+hand+muscle+involvement+in+amyotrophic+lateral+sclerosis+detected+by+motor+unit+number+estimates.">Dissociated small hand muscle involvement in amyotrophic lateral sclerosis detected by motor unit number estimates.</a> Muscle Nerve. 22, 870-873 (1999).</li><li>Menon, P., Kiernan, M. 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The present study reports on the diagnostic utility of the split hand index in ALS, a novel neurophysiological diagnostic biomarker. The SI reliably distinguished ALS from neuromuscular disorders, with an optimal diagnostic cut-off value of 5.2. The reduction in the SI was most prominent in limb-onset ALS patients. Importantly, a substantial proportion of ALS patients that were classified in the diagnostic &#8220;possible&#8221; category as per the recently developed diagnostic criteria11, exhibited an abnorma...

The split&#160;hand, refers to preferential atrophy of the thenar complex group of intrinsic hand muscles [abductor pollicis brevis (APB) and first dorsal interosseous (FDI)], with relative preservation of hypothenar muscles, and is a specific and early clinical feature of amyotrophic lateral sclerosis (ALS)1-4. The finding that the split hand sign is specific for ALS, suggests a potential role for the split hand sign as a diagnostic biomarker in ALS3.
Quantification of the split&#160;hand sign, through the development of a novel neurophysiological biomarker, may further aid in ALS diagnosis. Specifically, the split&#160;hand index (SI), which quantifies the split&#160;hand phenomenon, is derived by multiplying the compound muscle action potential (CMAP) amplitude recorded over the thenar complex muscles (APB and FDI), and dividing this product by the CMAP amplitude recorded over the hypothenar muscles (namely the abductor digiti minimi, ADM)5.
The diagnosis of ALS relies largely on clinically based criteria encompassing a combination of upper and lower motor neuron signs6. These criteria, however, were deemed insensitive especially in establishing a diagnosis of ALS in the early stages of the disease process7-10. A recent modification of the diagnostic criteria were developed11, and although these criteria appear to increase the diagnostic sensitivity12-16, the increase sensitivity seems restricted to bulbar-onset ALS patients15.
In the absence of a pathognomonic test, the diagnosis of ALS may be significantly delayed8. Ultimately, the institution of neuroprotective therapies and recruitment into clinical trials may be delayed, perhaps beyond the critical therapeutic window period9,17. Consequently, the diagnostic utility of the SI was prospectively assessed in sporadic ALS patients.

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			<td height="20" style="height:20px;width:125px;"></td>
			<td style="width:120px;"></td>
			<td style="width:136px;"></td>
			<td style="width:203px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Abrasive gel (Nu Prep)</td>
			<td>Weaver and Company</td>
			<td>N-TA\/P\H-3 ENG</td>
			<td>Skin preperation</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.doweaver.com)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Alcohol wipe</td>
			<td>Triad Disposables</td>
			<td>103101</td>
			<td>Skin preperation</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.triad-group.net)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Recording gel (Ten20 Conductive gel)</td>
			<td>Weaver and Company</td>
			<td>N-TA\/P\H-3 ENG</td>
			<td>Recording motor responses</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.doweaver.com)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Amyotrophic lateral sclerosis rating scale-revised questionnaire</td>
			<td>Publication&#160;</td>
			<td>Experimental builder</td>
			<td>Stage disease</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(see Methods and References)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Medical Research Council muscle strength scale</td>
			<td>Medical Research Council-UK</td>
			<td>Experimental builder</td>
			<td>Stage disease</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(see Methods and References)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
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			<td></td>
			<td></td>
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			<td colspan="2" height="20" style="height:20px;">Table of equipment used</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Name of the equipment used</td>
			<td>Company</td>
			<td>Catalog number</td>
			<td>Comments</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Nerve conduction machine (Synergy/Nicolet EDX)</td>
			<td>CareFusion (www.carefusion.com/medical-products/neurology)</td>
			<td>SA110106M</td>
			<td>To measure split hand index</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Synergy software</td>
			<td>CareFusion</td>
			<td>765654679</td>
			<td>To measure split hand index</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="3">(www.carefusion.com/medical-products/neurology)</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Tem millimeter gold cup disc electrodes</td>
			<td>Grass Technologies</td>
			<td>F-E5GH-60</td>
			<td>To record motor responses</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.grasstechnologies.com)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Neural earth plate</td>
			<td>Westmead Hospital</td>
			<td>Experimental builder</td>
			<td>To record limb temperature</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Thermometer</td>
			<td>Westmead Hospital</td>
			<td>Experimental builder</td>
			<td>To record limb temperature</td>
		</tr>
	</tbody>
</table>

utility of dissociated intrinsic hand muscle atrophy in the diagnosis of amyotrophic lateral sclerosis

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A novel split hand index (SI) was developed to quantify the split hand phenomenon, and its diagnostic utility was assessed in ALS patients. The split hand index was derived by dividing the product of the compound muscle action potential (CMAP) amplitude recorded over the abductor pollicis brevis and first dorsal interosseous muscles by the CMAP amplitude recorded over the abductor digiti minimi muscle. In order to assess the diagnostic utility of the split hand index, ALS patients were prospectively assessed and their results were compared to neuromuscular disorder patients. The split hand index was significantly reduced in ALS when compared to neuromuscular disorder patients (P&#60;0.0001). Limb-onset ALS patients exhibited the greatest reduction in the split&#160;hand index, and a value of 5.2 or less reliably differentiated ALS from other neuromuscular disorders. Consequently, the split&#160;hand index appears to be a novel diagnostic biomarker for ALS, perhaps facilitating an earlier diagnosis.

Clinical Phenotype
In total, 44 ALS patients were studied, of which 76% (N=33) were classified as definite or probable and 24% (N=11) as possible ALS according to the Awaji criteria11. The diagnosis of ALS was confirmed in the &#8220;possible&#8221; cohort after extensive investigations and clinical follow-up for up to 3 years and 53% died during this period. Bulbar-onset disease was evident in 41%, while limb-onset in 59% of ALS patients. At the time of assessment, mean dise...

Watch this Scientific Journal Video about Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis at JoVE.com

Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis

Dissociated atrophy of intrinsic hand muscles, termed the split hand, appears to be a specific feature of amyotrophic lateral sclerosis (ALS).&#160;Consequently, a novel neurodiagnostic test, termed the split hand&#160;index, was developed to quantify the clinical phenomenon of the split hand, which differentiated ALS from mimic disorders.

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A ...

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