Criteria for early detection of conduction block in multifocal motor ...

J Neurol (1997) 244 : 625–630 © Springer-Verlag 1997

Alberto Cappellari Eduardo Nobile-Orazio Nicoletta Meucci Giulia Levi Minzi Guglielmo Scarlato Sergio Barbieri

Received: 31 December 1996 Received in revised form: 1 August 1997 Accepted: 13 August 1997

A. Cappellari · E. Nobile-Orazio · N. Meucci · G. Levi Minzi · G. Scarlato · S. Barbieri (Y) Institute of Clinical Neurology, University of Milan, IRCCS Ospedale Maggiore Policlinico, Pad. Ponti, Via Francesco Sforza 35, I-20122 Milano, Italy Tel.: 2/55033818, Fax: 2/55190392

O R I G I N A L C O M M U N I C AT I O N

Criteria for early detection of conduction block in multifocal motor neuropathy (MMN): a study based on control populations and follow-up of MMN patients

Abstract Motor conduction block (MCB) has been used as the main diagnostic criterion in multifocal motor neuropathy (MMN). Nonetheless, no agreed definition of block currently exists; the proposed required percent decrement of proximal compound muscle action potential (CMAP) amplitude varies from > 20% to > 50%. The aim of this work was to evaluate, through a follow-up study of patients with MMN, the behaviour of MCB over time. The percent decrement and temporal dispersion of proximal CMAP have also been calculated in normal controls and in patients affected by amyotrophic lateral sclerosis (ALS). The results show that MCB in patients with MMN is a dynamic entity which greatly varies over time and that a > 50% CMAP amplitued reduction may well be

Introduction Multifocal motor neuropathy (MMN) is characterized by a progressive, asymmetric lower motor neuron weakness with or without mild sensory involvement [8, 19, 21]. Early diagnosis of MMN is important because it often responds to treatment [4, 5, 6, 7, 14, 15]. Although the presence of motor conduction block (MCB) is considered an essential feature of MMN, no agreed definition of MCB currently exists [17]. Detailed electrophysiological findings before and after intravenous immunoglobulin (IVIg) treatment have been reported [4], but there have been no studies to date on the spontaneous or treatment-induced variations of the neurophysiological parameters over time in this condition.

preceded by a smaller decrement that is nonetheless indicative of focal myelin damage in the appropriate clinical context. This datum and the results obtained in the control group and in patients with ALS suggest that a reappraisal of the diagnostic criteria for MCB, in cases with clinical and electrophysiological data strongly indicative of MMN, should be considered. Since MMN is a treatable disorder, the use of the proposed less restrictive criteria for the identification of MCB could allow for a promp and more effective treatment. Key words Multifocal motor neuropathy · Amyotrophic lateral sclerosis · Electrophysiological follow-up · Conduction block · Diagnostic criteria

The data obtained in a 3- to 4-year follow-up of patients with MMN were reviewed to evaluate the variability of MCB over time. Moreover, 40 normal controls and 20 patients with amyotrophic lateral sclerosis (ALS) were studied to investigate the proximal compound muscle action potential (CMAP) amplitude decrement and dispersion in different nerves.

Patients and methods The following cases have already been reported in a previous paper [15] and have been selected from a group of nine patients with MMN because of the great variability of the block over time. In the remaining patients, the block variability was also very prominent although limited to fewer nerves.

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The diagnosis of MMN was based on the presence of clinical and electrophysiological evidence of a progressive asymmetric motor neuropathy, with or without mild sensory involvement, with MCBs in two or more motor nerves outside the common sites of entrapment. Electrophysiological studies Nerve conduction studies and needle electromyography (EMG) of the proximal and distal muscles of the lower and upper limbs and muscles innervated by the cranial nerves were performed systematically over a 3- to 4-year period (always by S.B. and A.C; each individual patient was always examined by the same investigator). Sensory responses were evaluated in the median, ulnar and sural nerves, by measuring peak–peak amplitude and conduction velocities. Bilateral median, ulnar, peroneal and tibial motor nerves were studied in all patients. The median nerve was stimulated at the wrist, elbow and Erb’s point; the ulnar nerve at the wrist, elbow, above the elbow and at Erb’s point; the peroneal nerve at the ankle, below and above the fibular head; and the tibial nerve at the ankle and popliteal fossa. Whenever a conduction block was detected, the “inching” technique was applied, if possible. Stimulation at Erb’s point and the popliteal fossa was performed with needle electrodes. Care was taken to ensure that the stimulus was supramaximal, considering that chronic demyleinating lesions can be associated with an increased threshold for excitation [4, 7], and to exclude the presence of anomalous innervations (Martin-Gruber anastomosis and accessory branch of the peroneal nerve). Negative peak amplitude and duration of the CMAP were recorded and the decrement was calculated as CMAP amplitude ratio of proximal versus distal responses. Forty normal subjects (aged 18–68 years, mean 41.7) acted as controls and the proximal CMAP amplitude decrement and dispersion were calculated for each individual nerve. Twenty patients (aged 27–81 years, mean 57.2) affected by ALS, with both definite upper and lower motor neuron signs, according to the clinical criteria of Younger [24], and widespread active denervation with normal nerve conduction studies (but for a reduced CMAP amplitude), according to Lambert’s criteria [10, 11], have also been studied and the data obtained from the median, ulnar and peroneal motor nerve conduction studies are reported here. Case reports Patient 1 A 30-year-old woman came to our attention complaining of difficulty in dorsiflexion of the right foot and calf cramps. These symptoms began at the age of 21 years. Weakness progressed in a stepwise fashion, spreading to the contralateral leg and then asymmetrically to the hands. The family history was negative. Examination at the age of 24 years showed weakness of the muscles innervated by the radial and ulnar nerves (right more than left) and by the peroneal nerves (left more than right). There was no atrophy of the involved muscles. Results of cerebrospinal fluid (CSF) studies were normal. Serum levels of anti-asialo-GM1 antibodies were slightly elevated. A significant worsening was observed after steroid treatment, meaning that the patient was not able to walk independently and could not functionally use her upper limbs. The IVIg treatment (0.4 g/kg for 5 consecutive days) was started on 8 April 1991. The same regimen was repeated after 2 months and was followed by a 2-day infusion (0.4 g/kg per day) every 4 weeks. In September 1991, oral cyclophosphamide 2 mg/kg per day was added. There was a progressive clinical improvement and no functional disability at the age of 29 years.

Patient 2 A 54-year-old woman developed, at the age of 46 years, a slowly progressive weakness of the right lower extremity with cramps spreading, over a 3-year period, to the contralateral lower limb. At the age of 50 years, her gait was unsteady and she complained of weakness and tingling in both hands. The family history was unremarkable. Physical examination revealed an asymmetric marked weakness of the lower limbs (distal more than proximal) and a mild weakness in the intrinsic muscles of the hands. Muscle wasting was evident only in the right leg. Results of CSF examination were normal. Serum levels of anti-asialo-GM1 antibodies were slightly elevated. A sural and peroneal motor nerve biopsy showed axonal degeneration. The IVIg treatment (0.4 g/kg for 5 consecutive days) was started on 27 August 1991. The same regimen for IVIg was repeated after 2 months and was followed by a 2-day infusion (0.4 g/kg per day) every 4 weeks. In December 1991, oral cyclophosphamide 1 mg/kg per day was added. An almost complete recovery of upper limb function was obtained, while gait improved even though a right foot steppage persisted. Patient 3 A 35-year-old man noticed, when he was aged 28 years, weakness and cramps in the right hand, spreading, over the following months, to the proximal right upper limb and to the lower limbs. The family history showed no abnormalities. At the neurological examination, he showed bilateral steppage, weakness of the intrinsic hand muscles and of the flexor and extensor muscles of the forearm, more pronounced in the right upper limb. No muscle atrophy was evident. Cramps were easily provoked by any willed movement. Results of CSF studies were normal. The serum antiganglioside antibodies titre was normal. The IVIg treatment (0.4 g/kg for 5 consecutive days) was started on 8 April 1991. The same regimen was repeated after 2 months and was followed by a 2-day infusion (0.4 g/kg per day) every 4 weeks. Cyclophosphamide was not tolerated. IVIg therapy did not result in a significant improvement of the clinical picture.

Results The results of motor nerve conduction studies are reported in Tables 1–3. Distal CMAP amplitude and percent decrement show a great variability over time. Since MCB is calculated as the percentage reduction of proximal versus distal CMAP amplitude, we have tried, whenever possible, to calculate the true variation of block over the same short nerve segment by selecting those sets of results in which the distal CMAP amplitude variation was negligible. In our control subjects and in others’ [2], the amplitudes of the maximum distal muscle reponses between successive examinations are within 10% of each other, when care is taken to avoid technical errors. For instance, in case 1, the distal CMAP amplitude of the right median nerve was 8.4 mV in May 1992 and 9.3 mV in August 1994, with a CMAP decrement at elbow stimulation of 51.2% and 25.3%, respectively. In case 2, the distal CMAP amplitude of the right median nerve was 8.0 in September 1991 and 8.1 in November 1991, but the decrement at elbow stimulation went from 12.5% to 54.3%. Similarly, in case 3, the distal CMAP amplitude of the right median nerve was 10.5 mV,

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Table 1 Motor conduction studies in case 1 (female, 30 years) (CMAP compound muscle action potential, AmpP proximal CMAP amplitude evoked by stimulation at the elbow (median) or slightly distal to the elbow (ulnar), AmpD distal CMAP amplitude, --- not done, Decr proximal CMAP amplitude reduction, CV conduction velocity. Maximal and minimal distal CMAP amplitude and percentage proximal CMAP amplitude decrement values are underlined Date

AmpD (mV)

Decr (%)

CV (m/s)

Abductor pollicis brevis muscle Right median nervea 19 Mar 1991 2.7 18 Apr 1991 1.3 4 Jun 1991 2.4 18 Jun 1991 2.1 26 Nov 1991 1.6 21 May 1992 4.1 6 May 1993 4.6 3 Aug 1994 6.2

6.8 6.0 10.0 10.7 7.6 8.4 8.4 8.3

60.3 78.3 76.0 80.4 78.9 51.2 45.2 25.3

53.5 55.9 54.1 52.9 48.5 50.0 50.9 56.0

Abductor pollicis brevis muscle Left median nervea 19 Mar 1991 0.30 18 Apr 1991 0.65 4 Jun 1991 3.3 18 Jun 1991 2.0 26 Nov 1991 0.53 21 May 1992 5.2 6 May 1993 8.8 3 Aug 1994 5.5

1.5 1.8 6.6 4.0 1.2 6.0 9.5 6.2

80.0 63.9 50.0 50.0 55.8 13.3 7.4 11.3

31.1 59.4 62.9 58.5 51.1 55.4 57.6 52.0

Abductor digiti minimi muscle Rigth ulnar nerveb 16 Jul 1990 4.0 19 Mar 1991 2.3 18 Apr 1991 0.78 4 Jun 1991 0.45 18 Jun 1991 1.4 26 Nov 1991 0.74 21 May 1992 2.4 6 May 1993 1.5 3 Aug 1994 1.8

4.5 3.4 3.0 3.1 2.0 1.9 2.4 1.9 2.7

11.1 32.4 74.0 85.5 30.0 61.1 0.0 21.1 33.3

39.2 33.1 52.9 49.5 42.5 36.6 37.5 43.5 44.5

Abductor digiti minimi muscle Left ulnar nerveb 16 Jul 1990 --19 Mar 1991 3.8 18 Apr 1991 4.1 4 Jun 1991 7.1 18 Jun 1991 6.9 26 Nov 1991 9.6 21 May 1992 8.8 6 May 1993 7.9 3 Aug 1994 8.4

--3.8 4.8 8.3 7.8 10.0 9.0 7.9 11.0

--0.0 14.6 14.5 11.5 4.0 2.2 0.0 23.6

68.1 58.1 61.6 57.7 55.1 61.1 59.7 60.8

a Median

AmpP (mV)

nerve: CMAP dispersion (proximal/distal) is never greater than 5.6% b Ulnar nerve: CMAP dispersion (proximal/distal) is never greater than 6.3%

Table 2 Motor conduction studies in case 2 (female, 54 years). Maximal and minimal distal CMAP amplitude and percentage proximal CMAP amplitude decrement values are underlined Date

AmpP (mV)

AmpD (mV)

Decr (%)

CV (m/s)

Abductor pollicis brevis muscle Right median nervea 22 Aug 1991 2.6 4 Sep 1991 7.0 14 Nov 1991 3.7 26 Nov 1991 4.4 13 Feb 1992 6.2 7 Sep 1992 6.1 21 Oct 1993 3.4 26 Sep 1994 2.1

6.9 8.0 8.1 9.0 9.0 12.8 7.6 5.8

62.3 12.5 54.3 51.1 31.1 52.3 55.3 63.8

55.6 55.9 51.1 56.8 55.0 53.1 55.8 53.8

Abductor pollicis brevis muscle Left median nervea 22 Aug 1991 3.7 4 Sep 1991 5.0 14 Nov 1991 3.6 26 Nov 1991 6.4 13 Feb 1992 6.8 7 Sep 1992 5.5 21 Oct 1993 5.9 26 Sep 1994 4.5

6.1 7.8 6.6 8.6 9.5 7.5 7.3 7.6

39.3 35.9 45.5 25.6 28.4 26.7 19.2 40.8

53.6 53.0 51.4 50.0 53.2 50.0 47.4 47.5

Abductor digiti minimi muscle Right ulnar nerveb 22 Aug 1991 2.7 4 Sep 1991 8.2 14 Nov 1991 6.2 26 Nov 1991 6.7 13 Feb 1992 9.0 7 Sep 1992 7.8 21 Oct 1993 5.3 26 Sep 1994 5.8

6.2 9.0 8.8 8.8 11.7 11.5 9.5 10.0

56.5 8.8 29.5 23.9 23.1 32.2 44.2 42.0

55.4 55.7 52.5 56.0 57.9 51.9 60.0 56.6

Abductor digiti minimi muscle Left ulnar nerveb 22 Aug 1991 8.1 4 Sep 1991 --14 Nov 1991 7.2 26 Nov 1991 7.9 13 Feb 1992 8.9 7 Sep 1992 8.8 21 Oct 1993 11.1 26 Sep 1994 9.4

8.3 --7.7 8.3 8.9 9.1 12.8 11.0

2.4 --6.5 4.8 0.0 3.3 3.3 14.5

43.3 --53.7 59.5 58.3 59.1 59.4 57.5

a Median nerve: CMAP dispersion (proximal/distal) never greater than 5.7% b Ulnar nerve: CMAP dispersion (proximal/distal) never greater than 5.9%

both in January 1989 and in February 1991, while the CMAP decrement evoked by stimulation at the elbow varied from 23.8% to 88.6% (other examples can be extracted from the tables).

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Table 3 Motor conduction studies in case 3 (male, 35 years). (AmpP proximal CMAP amplitude evoked by stimulation at the elbow (median), slightly distal to the elbow (ulnar) or slightly distal to the knee (peroneal) Maximal and minimal distal CMAP amplitude and percentage proximal CMAP amplitude decrement values are underlined Date

AmpP (mV)

Abductor pollicis brevis muscle Right median nervea 20 Jan 1989 8.0 14 Feb 1991 1.2 18 Apr 1991 1.1 4 Jun 1991 1.8 8 Jun 1991 1.6 30 Jul 1991 1.9 20 Feb 1992 2.1 15 Jun 1992 1.8 11 Feb 1993 0.60 13 Dec 1993 0.26 Abductor pollicis brevis muscle Left median nervea 20 Jan 1989 --14 Feb 1991 1.1 18 Apr 1991 1.5 4 Jun 1991 2.9 8 Jun 1991 1.8 30 Jun 1991 --20 Feb 1992 2.1 15 Jun 1992 1.6 11 Feb 1993 1.2 13 Dec 1993 2.6 Extensor digitorum brevis muscle Right common peroneal nerveb 20 Jan 1989 --14 Feb 1991 3.4 18 Apr 1991 1.9 4 Jun 1991 5.6 18 Jun 1991 6.1 30 Jul 1991 --20 Feb 1992 5.5 15 Jun 1992 6.6 11 Feb 1993 6.2 13 Dec 1993 6.1 Abductor digiti minimi muscle Right ulnar nervec 20 Jan 1989 8.0 14 Feb 1991 2.5 18 Apr 1991 2.0 4 Jun 1991 2.1 18 Jun 1991 1.7 30 Jul 1991 2.0 20 Feb 1992 2.2 15 Jun 1992 3.3 11 Feb 1993 2.7 13 Dec 1993 2.6

AmpD (mV)

Decr (%)

CV (m/s)

10.5 10.5 10.0 16.9 13.8 15.6 15.6 17.7 16.2 16.0

23.8 88.6 89.0 89.3 88.4 87.8 86.5 89.8 96.3 98.4

43.4 39.5 42.6 38.1 43.1 42.1 47.4 39.3 41.6 37.8

--16.0 16.6 19.5 15.2 --22.0 19.7 16.9 22.4

--4.0 4.0 7.2 8.8 --10.6 9.3 11.0 8.8

10.6 9.6 10.0 8.4 8.1 8.1 11.4 10.1 11.3 9.3

--93.1 91.0 85.1 88.2 --90.5 91.9 92.9 88.4

--15.0 52.5 22.2 30.7 --48.1 29.0 43.6 30.7

24.5 69.8 80.0 75.0 79.0 75.3 80.7 67.3 66.1 72.0

--40.5 33.9 37.0 37.0 --33.1 38.4 30.9 39.7

--40.5 38.5 38.8 41.7 --38.0 45.6 39.7 37.7

39.5 34.5 36.8 33.4 36.2 34.8 34.9 35.8 33.7 34.5

a Median nerve: CMAP dispersion (proximal/distal) never greater than 2.3% b Peroneal nerve: CMAP dispersion (proximal/distal) never greater than 7.9% c Ulnar nerve: CMAP dispersion (proximal/distal) never greater than 2.1%

The percent decrement variability, which is sometimes very relevant, did not always correlate with IVIg therapy. For instance, in case 3 (Table 3), the proximal CMAP amplitude decrement varies from 23.8% to 88.6% in the right median nerve and from 24.5% to 69.8% in the right ulnar nerve, after stimulation slightly distal to the elbow, at examinations performed in January 1989 and February 1991, which preceded any treatment. In case 1, the proximal CMAP amplitude decrement varies from 11.1% to 32.4% in the right ulnar nerve (evoked by stimulation Table 4 Data obtained in 40 control subjects: 14 females and 26 males, mean age 41.7 years (range 18–68). (Dur D distal CMAP duration, Disp proximal CMAP dispersion, Lat D distal latency) Amp D (mV)

Decr (%)

Disp (%)

Lat D (ms)

CV (m/s)

Median Mean Min. Max.

10.7 5.8 16.2

4.9 1.6 8.9

4.4 0.0 13.8

3.5 2.6 4.3

59.0 50.0 64.7

Ulnar Mean Min. Max.

11.4 8.3 14.1

5.8 1.0 9.3

4.4 0.0 11.8

2.7 2.1 4.2

61.1 50.4 68.5

Peroneal Mean Min. Max.

7.9 3.5 14.0

7.3 0.0 22.9

7.4 0.0 17.5

4.1 3.2 5.5

47.8 41.3 56.1

Tibial Mean Min. Max.

14.5 7.5 24.6

15.4 7.2 22.7

9.3 1.7 21.1

4.2 3.3 5.8

45.8 40.3 55.3

Table 5 Data obtained in 20 patients with amyotrophic lateral sclerosis (ALS). 8 females and 12 males, mean age 57.2 years (range 27–81) Amp D (mV)

Decr (%)

Disp (%)

Lat D (ms)

CV (m/s)

Median Mean Min. Max.

4.7 0.3 13.0

2.7 0.0 13.3

2.0 0.0 8.7

4.5 3.2 7.8

49.5 40.5 60.5

Ulnar Mean Min. Max.

5.8 0.4 10.0

5.2 0.0 15.2

2.7 0.0 10.0

3.1 2.0 5.6

52.0 39.2 65.8

Peroneal Mean Min. Max.

2.9 0.1 6.8

9.9 0.0 29.4

6.2 0.0 17.9

5.6 4.0 8.0

42.2 31.4 48.2

Tibial Mean Min. Max.

3.7 0.5 7.5

19.5 5.5 40.5

9.2 3.4 24.8

6.4 4.8 8.4

43.4 40.9 55.8

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slightly distal to the elbow) at controls performed in July 1990 and March 1991 before any treatment was started. The mean and range of the percentage decrement and dispersion of the proximal CMAP of the median, ulnar, peroneal and posterior tibial nerves in normal controls and in patients with ALS are shown in Tables 4 and 5, respectively. In normal controls, the maximal decrement and dispersion of proximal CMAP was 8.9% and 13.8% for the median, 9.3% and 11.8% for the ulnar, 22.9% and 17.5% for the peroneal and 22.7% and 21.1% for the tibial nerve. In patients with ALS, the maximal decrement and dispersion was 13.3% and 8.7% for the median, 15.2% and 10.0% for the ulnar, 29.4% and 17.9% for the peroneal and 40.5% and 24.8% for the tibial nerve. In both control groups, the proximal CMAP was evoked at the usual sites of stimulation.

Discussion The diagnosis of MMN is based on the electrodiagnostic evidence of multifocal motor demyelination with MCBs. Unfortunately, there are no uniformly accepted criteria for the identification of conduction block. Some authors use a greater than 20% drop in the peak–peak amplitude of the CMAP with a less than 15% change in the negative peak duration [2], while others use a less than 50% reduction in the CMAP amplitude and area [4, 22], with a less than 15% change in the negative peak duration [4], and others still believe that different criteria should be used in diagnosing conduction block and abnormal temporal dispersion in different nerves [16]. In our cases, both the distal CMAP amplitude and the proximal CMAP percent decrement vary over time. The variability of the distal CMAP amplitude suggests the possible presence of a conduction block beyond the most distal site of stimulation [3]. This has already been taken into consideration in patients with Guillain-Barré syndrome [2] and is important in the evaluation of the percent decrement of proximal CMAP. Since conduction block is usually calculated as percent reduction of proximal versus distal CMAP amplitude, in the absence of temporal dispersion, the percent block may not correspond to the absolute value of the block if the distal CMAP amplitude varies independently from the proximal one. Therefore, an unchanging distal CMAP amplitude would be necessary to obtain a reliable measure of percentage block at follow-up. The variation of block over time should then be calculated as a percent reduction of proximal CMAP amplitude versus a fixed value of distal CMAP amplitude. Our findings show that conduction block is a dynamic entity with possible evolution from a minor to a major block. Therefore, diagnostic criteria, such as those we have used in our previous paper (40% reduction for all nerves) [15] or those proposed by Rhee [22], although

methodologically correct, could be too strict when applied to patients with signs and symptoms strongly suggestive of MMN; even though they reduce false-positive results due to phase cancellation of potentials, they do not take into consideration those values which might become significant at follow-up. A greater than 50% amplitude reduction as diagnostic criterion for conduction block has been used among others also by some authors who nonetheless criticize it as being too restrictive and underly the need for further studies on normal and control subjects with other diseases [12]. Moreover, other authors, describing patients with the clinical phenotype of MMN without conduction block at EMG examination [18], and claiming that conduction block should not be considered an essential criterion for MMN [23] used the strictest criteria for the identification of the block. Indeed, the application of less restrictive criteria to their cases shows that conduction blocks are present. This is also important because conduction block is the hallmark of focal myelin damage and is helpful in distinguishing MMN from other demyelinating nerve disorders that have a different response to treatment [i.e. steroids are beneficial in chronic inflammatory demyelinating polyneuropathy (CIDP) but very rarely so in MMN]. When an abnormal amplitude reduction in the proximal CMAP owing to temporal dispersion is present in conditions that cause chronic partial denervation, such as motor-neuron disease [13], conduction block cannot be reliably assessed [9]. In our ALS cases, as well as in a larger study performed on 133 patients [1], the motornerve conduction abnormalities never approached levels suggestive of demyelination and MCBs were not evident. Also, in the distal lower motor neuron syndromes, which are clinically similar to MMN, no MCB were observed in neurophysiological studies [20]. The results obtained in patients with MMN, ALS and in normal controls suggest an opportunity of a reappraisal of the criteria for the early detection of conduction block in those patients in which clinical (limitation of weakness to the distribution of one or more named peripheral nerves, minimal amount of wasting for the degree of weakness at the beginning of the disease) and electrophysiological (possibility to evoke motor-unit action potentials with electrical stimulation at a distal site which a cooperative patient is unable to activate voluntarily, relatively scarce active denervation in the involved muscles in the early stages of the disease) findings are strongly suggestive of MMN. As MCB is a dynamic entity which greatly varies over time, a greater than 50% proximal CMAP amplitude reduction may well be preceded by a smaller decrement that is nonetheless indicative of focal myelin damage in the appropriate clinical context. When the values in patients exceeded the normal mean+3SD, the values were considered to be abnormal. If, nonetheless, the data obtained in ALS patients are considered, although block can be present in this condition, we feel that a more cautious

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approach should be used. Therefore, when dealing with a patient with a clinical phenotype clearly indicative of MMN, a conduction block should be suspected when the proximal CMAP amplitude reduction is greater than 15% for the median and greater than 20% for the ulnar nerve, with a proximal CMAP dispersion of less than 15% greater than 35% for the peroneal and greater than 50%

for the tibial nerve with a proximal CMAP dispersion of less than 25%. Since MMN is a potentially treatable disorder, increased diagnostic sensitivity of the neurophysiological tests could allow a prompt and more effective treatment and prevent, if possible, atrophy of the involved muscles secondary to the axonal loss.

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