- Email: [email protected]
Cranial nerve involvement as presenting sign of multifocal motor neuropathy
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1733–1735 10. Komiyama M, Nakajima H, Nishikawa M, et al. Middle cerebral artery variations: duplicated and accessory arteries. AJNR Am J Neuroradiol 1998;19:45–9. 11. Lasjaunias P, Berenstein A. Internal carotid artery (ICA) anterior division. Surgical neuroangiography III. Berlin, Germany: Springer-Verlag; 1990. p. 111–151. 12. Villablanca JP, Rodriguez FJ, Stockman T, et al. MDCT angiography for detection and quantification of small intracranial arteries: comparison with conventional catheter angiography. AJR Am J Roentgenol 2007;188:593–602.
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13. Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology 1989;39:1246–50. 14. Fahey CD, Alberts MJ, Bernstein RA. Oral clopidogrel load in aspirin-resistant capsular warning syndrome. Neurocrit Care 2005;2:183–4. 15. Lalive PH, Mayor I, Sztajzel R. The role of blood pressure in lacunar strokes preceded by TIAs. Cerebrovasc Dis 2003;16:88–90. 16. Teng HW, Hong CT. Capsular warning syndrome: report of a case. Acta Neurol Taiwan 2008;17:248–52.
doi:http://dx.doi.org/10.1016/j.jocn.2011.12.030
Cranial nerve involvement as presenting sign of multifocal motor neuropathy Giuliana Galassi a,⇑, Giovanna Albertini b, Franco Valzania a, Alberto Barbieri b a b
Department of Neurosciences, Via P. Giardini, 1350, University of Modena and Reggio Emilia, 41010 Modena, Italy 2nd Intensive Care Unit, University of Modena & Reggio Emilia, Italy
a r t i c l e
i n f o
Article history: Received 12 October 2011 Accepted 28 December 2011
Keywords: Acute inflammatory demyelinating polyneuropathy Cranial nerve palsy Conduction block Multifocal motor neuropathy
a b s t r a c t Multifocal motor neuropathy (MMN) is characterized by slowly progressive, predominantly distal, asymmetric limb weakness and partial conduction blocks (CB) of motor axons. Cranial nerve involvement and respiratory failure are uncommon. We report two patients who exhibited unilateral hypoglossal and abducens palsy as presenting signs. Other remarkable features were autonomic instability and respiratory failure due to bilateral phrenic nerve involvement. Treatment with intravenous (IV) immunoglobulin (Ig) resulted in an improvement. Patient 2, who showed IgM reactivity against ganglioside GM1, has been receiving maintenance therapy with IVIg for 7 years. We speculate that cranial weakness of our patients could be due to CB similar to those detected in the motor nerves of the extremities. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Multifocal motor neuropathy (MMN) is characterized by slowly progressive, asymmetric limb weakness, with minimal or no sensory symptoms.1,2 Diagnostic criteria include a partial conduction block (CB) of motor axons at sites that are uncommon for compression or entrapment.1,2 A CB is defined as equal or greater than 50% reduction in the compound muscle action potential (CMAP) amplitude or at least 40% reduction in area between proximal and distal stimulation in nerves with a temporal dispersion of less than 30%.1,2 Cranial nerve weakness is an uncommon presenting sign of MMN.1–5
2. Case reports 2.1. Patient 1 A 64-year-old man was admitted after a 2-month history of hand cramping, shortness of breath, and abdominal distension. On admission, he presented left-sided tongue palsy with fasciculation, without pharyngeal weakness. He was able to walk; the upper and lower extremity strength was scored 4/5 proximally, and 3/5 distally on the Medical Research Council (MRC) scale. His deep reflexes were weakened in the upper, and were absent in the lower limbs. Sensation was intact. Stool cultures excluded Campylobacter jejuni infection. Within 5 days, the weakness progressed to an asymmetric tetraparesis, with his distal strength graded between 1/5 and 2/5 in his upper and lower limbs. Anti-ganglioside GM1,1,2 anti-acetylcholine receptor antibody assays (on days 9 and 15) were negative. Respiratory insufficiency required supple⇑ Corresponding author. Tel.: +39 059 4225573; fax: 39 059 4223898. E-mail address: [email protected] (G. Galassi).
mentary oxygen therapy and monitoring in the intensive care unit (ICU). Phrenic nerve involvement was confirmed by the bilateral absence of CMAP from diaphragm muscle. Cerebrospinal fluid (CSF) examination (days 5, 7, and 23) showed normal protein content and no cells. Routine laboratory tests were unremarkable. Electrophysiology (days 5, 8, and 17) showed definite CB1,2 at the axilla–elbow, elbow–wrist, and popliteal fossa–ankle segments of the median, ulnar, and tibial nerves. F-waves were not delayed, except in the tibial nerve. Distal latencies and velocity across segments with CB were within normal limits. Sensory conduction studies of ulnar, median, and sural nerves were normal. The concentric needle electromyography (EMG) demonstrated acute and chronic partial denervation in multiple muscles. The patient declined tongue and paraspinal EMG. Intravenous immunoglobulin (IVIg, 0.4 g/kg for 5 days) was given. He exhibited progressive recovery from the 3rd week and onward, becoming able to stand unaided. Eighteen weeks after initial onset, his tongue and extremity weakness relapsed with the same intensity. An IVIg course was given monthly (0.4 g/kg for 5 days) for 6 months. Electrodiagnostic studies at 5 and 7 months confirmed CB in 6 of 8 tested motor nerves. Table 1 shows serial electrophysiological results for patient 1. Twenty eight weeks after onset, the patient was areflexic with strength scored 3/5 proximally in the upper limbs, 1/5 in the wrist extensors, intrinsic hand, and feet muscles. His clinical condition worsened due to septic shock in the 8th month of his illness. 2.2. Patient 2 A 32-year-old woman awoke with horizontal diplopia on right lateral gaze and paresthesias in the dorsal aspects of her left lower limb and right hand. No preceding illnesses were reported. Neurological evaluation revealed right-sided abducens and hypoglossal
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Case Reports / Journal of Clinical Neuroscience 19 (2012) 1733–1735
Table 1 Serial electroneurography of patient 1 with hypoglossal weakness Motor nerve studyA
1 month
5 months
7 months
Normal limits in controls
Right median Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, E–W) Minimal F-wave latency (ms)
3.5 4.0/2.1 60.0 24.6
3.6 6.0/1.5 52.3 27.8
3.3 6.1/4.0 56.5 30.0
64 >4 >49 631
Right ulnar Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, BE–W) Minimal F-wave latency (ms)
3.1 7.8/2.0 56.8 27.0
3.0 6.2/3.0 54.1 28.6
2.6 7.6/1.8 52.2 29.4
64 >6 >49 631
Right tibial Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, PF–A) Minimal F-wave latency (ms)
5.8 6.0/2.1 45.7 47.9
5.2 4.0/2.0 42.2 46.7
3.5 6.3/1.5 43.7 52.9
66 >3 >46 645
Sites of CB and % changes in CMAP amplitude at diagnosis Axilla–elbow, E–W (55–57%)
Axilla–above elbow, BE–W (50–64%)
PF–A (>60%)
CB = conduction block, CMAP = compound muscle action potential, D/P = distal/proximal, E–W = elbow–wrist, BE–W = below elbow–wrist, PF–A = popliteal fossa–ankle. A Recording sites were the abductor pollicis brevis (median), abductor digiti minimi (ulnar), and abductor hallucis longus (tibial).
palsy and deep areflexia. CSF, edrophonium chloride (the Tensilon test), MRI, and her visual-evoked responses were normal. The cranial deficits fully recovered within 1 week. After 1 month, the diplopia and tongue weakness relapsed associated with 3/5 weakness in the right ulnar, left peroneal and tibial distributions. CB were detected in the axilla–elbow, elbow–wrist, and popliteal fossa–ankle segments of the right median, both ulnar, right peroneal and tibial nerves;1,2 median and ulnar sensory conductions recorded concurrently over identical nerve segments were normal. The anti-GM1 IgM titer was elevated 7 times greater than normal limits.1,2 There was no response to oral prednisone. Repeated IVIg (2 g/kg every 2 months) improved ocular, tongue, and extremity strength, which stabilized to 2/5 to 3/5 throughout. Ophthalmoplegia and tongue weakness showed exacerbations during the 7 years of follow-up. At 87 months after her first presentation, CB were found in the median, ulnar, peroneal, and tibial nerves. Table 2 shows this patient’s serial electroneurographic results; conduction velocity in the motor nerves showed minimal slowing. CMAP showed less than 30% temporal dispersion, differing from that expected in chronic inflammatory demyelinating polyneuropathy (CIDP).1,2
3. Discussion We report two patients with MMN1,2 with unilateral cranial nerve involvement as presenting signs. Neither patient had preceding infections or abnormal haematological tests. The remarkable features were relapsing weakness in arms and legs, bilateral phrenic nerve involvement, and dysautonomia in patient 1. CBs were confined to the extremity motor nerves and persisted on consecutive studies which showed a dramatic selectivity of the condition for motor axons, with normal sensory conduction identified in the same segments as the motor neuropathy.1,2 This feature differentiated the disorder from CIDP.1,2 In addition, our patients did not show the physiological consequences of demyelination commonly observed in CIDP, such as prolonged distal motor latencies, marked conduction slowing, and excessive temporal dispersion.1,2 Repeated IVIg, unlike oral prednisone, provided some benefit. Clinical remission did not correlate with the electrophysiological reversal of CB.1,2 In both patients, the needle EMG showed chronic partial denervation at multiple sites. Patient 2 showed IgM reactivity against GM1.1,2 Our initial diagnosis of Guillain Barre’ syndrome (GBS) was based on a subacute onset of cranial and oculomotor
Table 2 Serial electroneurography of patient 2 with abducens and hypoglossal weakness Motor nerve studyA
1 month
51 months
87 months
Normal limits in controls
Right median Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s E–W) Minimal F-wave latency (ms)
4.2 16.0/4.4 52.0 46.5
3.4 9.5/3.0 43.8 35.6
3.2 8.8/4.6 42.0 38.2
64 >4 >49 631
Right ulnar Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, BE–W) Minimal F-wave latency (ms)
3.2 15.6/5.0 46.7 55.2
2.8 9.6/2.9 44.6 43.0
4.1 4.0/1.0 46.6 Absent
64 >6 >49 631
Right tibial Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, PF–A) Minimal F-wave latency (ms)
5.5 19.6/4.2 57.5 49.7
5.0 17.0/3.8 43.2 50.3
4.2 16.8/7.0 44.5 47.7
66 >3 >46 645
Sites of CB and % changes in CMAP amplitude at diagnosis Axilla–elbow, E–W (53–57%)
Axilla–above elbow, BE–W (66–70%)
PF–ankle (>60%)
CB = conduction block, CMAP = compound muscle action potential, D/P = distal/proximal, E–W = elbow–wrist, BE–W = below elbow–wrist, PF–A = popliteal fossa–ankle. A Recording sites were the abductor pollicis brevis (median), abductor digiti minimi (ulnar), and abductor hallucis longus (tibial).
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1733–1735
1735
Table 3 Reports of multifocal motor neuropathy with cranial nerve involvement Yearref
Age (years)* gender
Onset/evolution
Limb weakness distribution
Cranial nerve involvement
Antiboby/Ig isotype
Treatment
Clinical outcome
19869
38/M
Slow
Asymmetric
IX, X, XII
IgM anti-GM1
Not reported
3
1992
26/M
Slow
Asymmetric
Right XII
Normal
IVIg, steroid
19975
45/M
Acute in 8–10 days
Asymmetric
Not evaluated
Steroid, cyclophosphamide, PE
20017
46/M
Slow
Asymmetric
Bilateral VI and VII, left IV, XI, XII Bilateral III, IX, X
8
72/M
Slow
Asymmetric
Right XII
IgG, IgM antiGM1, anti-MAG IgM anti-GM1
IVIg, cyclophosphamide, PE, steroids,azathioprine IVIg
Quadriplegia, death (21 years) Improvement over 5 months Improvement over 15 months Quadriplegia, death (18 years) Improvement over 3 months
2002
*
Age at first symptom, F = female, GM1 = ganglioside GM1, IVIg = intravenous immunoglobulin, M = male, PE = plasma exchange.
weakness, respiratory failure, and autonomic dysfunction (patient 1). CSF examinations were normal. Involvement of the cranial motor or mixed nerves, such as the oculomotor, vagal, and hypoglossal nerves, is found in 26% to 61% of demyelinating GBS6; asymmetric cranial nerve palsy, if persistent (except for the facial nerve), is considered indicative of diagnoses other than GBS.4,6–9 In our patients, the diagnosis of GBS was challenged when the disease recurred greater than 3 times without full recovery in between.1,2 Ozaki et al.10 reported a 16-year-old boy with asymmetric weakness, abducens palsy, and a high titer of anti-GM1 antibodies; electrophysiology showed decreased velocity, CB, and temporal dispersion in motor and sensory axons, which fulfilled the diagnostic criteria of CIDP.1,2,10 Involvement of cranial nerves in MMN has been reported as initial sign only by two authors:5,8 ophthalmoplegia was the presenting symptom of Pringle case who subsequently developed multiple cranial nerve palsies.5 Hypoglossal neuropathy was the presenting sign of Axelsson’s patient8 and of another with Lewiss-Sumner syndrome masquerading as MND.4 Bulbar and diaphragm weakness were observed after 20 years of progressive disease;9 a patient of Kaji et al.3 developed hand and foot weakness followed by reversible tongue hemiatrophy several months later. Beydoun et al.7 reported bilateral ptosis and autonomic instability before death in a patient with secondary amyloidosis (Table 3). Cranial nerves are generally spared in MMN; bulbar involvement or cranial weakness are exclusion clinical criteria for MMN.1 However, the diagnosis of MMN should be considered when cranial weakness persists or relapses in association with multifocal CB. Cranial weakness could be due to chronic CB, similar to findings in the extremity motor nerves.5,8 The correct diagnosis doi:http://dx.doi.org/10.1016/j.jocn.2011.12.030
in such patients has clinical implications for treatment as well as for prognosis. Acknowledgements We thank Drs. K. Funakoshi and M. Odaka for the antiganglioside antibody assays performed at the Department of Neurology, Dokkyo University, Japan, in one of the patients reported. References 1. Van Schaik IN, Bouche P, Illa I, et al. European Federation of Neurological Societies/Peripheral nerve societies guidelines on management of multifocal motor neuropathy. Eur J Neurol 2006;13:802–8. 2. Chaundhry V, Corse AM, Cornblath DR, et al. Multifocal motor neuropathy: electrodiagnostic features. Muscle Nerve 1994;17:198–205. 3. Kaji R, Shibasaki H, Kimura J. Multifocal demyelinating motor neuropathy:cranial nerve involvement and immunoglobulin therapy. Neurology 1992;42:506–9. 4. Weiss MD, Oakley JC, Meekins GD. Hypoglossal neuropathy in Lewis-Sumner syndrome masquerading as motor neuron disease. Neurology 2006;67:175–6. 5. Pringle CE, Belden J, Veitch JE, et al. Multifocal motor neuropathy presenting as ophthalmoplegia. Muscle Nerve 1997;20:347–51. 6. Sakakibara Y, Mori M, Kuwabara S, et al. Unilateral cranial and phrenic nerve involvement in axonal Guillain-Barre’ syndrome. Muscle Nerve 2002;25:297–9. 7. Beydoun SR, Rison RA, Commins D. Secondary amyloidosis as a life ending event in multifocal motor neuropathy. Muscle Nerve 2001;24:1396–402. 8. Axelsson G, Leidholm LJ. Multifocal motor neuropathy-unusual cause of hypoglossal palsy. Lakartidningen 2002;99:1448–50. 9. Roth G, Rohr J, Magistris MR, et al. Motor neuropathy with proximal multifocal persistent conduction block, fasciculations and myokymia. Eur Neurol 1986;25:416–23. 10. Ozaki I, Baba M, Kurihara A, et al. Chronic inflammatory demyelinating polyneuropathy (CIDP) with ophthalmoplegia: a case with asymmetric limb weakness and high titers of anti-GM1 antibody. Eur J Neurol 1996;3:457–61.
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13. Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology 1989;39:1246–50. 14. Fahey CD, Alberts MJ, Bernstein RA. Oral clopidogrel load in aspirin-resistant capsular warning syndrome. Neurocrit Care 2005;2:183–4. 15. Lalive PH, Mayor I, Sztajzel R. The role of blood pressure in lacunar strokes preceded by TIAs. Cerebrovasc Dis 2003;16:88–90. 16. Teng HW, Hong CT. Capsular warning syndrome: report of a case. Acta Neurol Taiwan 2008;17:248–52.
doi:http://dx.doi.org/10.1016/j.jocn.2011.12.030
Cranial nerve involvement as presenting sign of multifocal motor neuropathy Giuliana Galassi a,⇑, Giovanna Albertini b, Franco Valzania a, Alberto Barbieri b a b
Department of Neurosciences, Via P. Giardini, 1350, University of Modena and Reggio Emilia, 41010 Modena, Italy 2nd Intensive Care Unit, University of Modena & Reggio Emilia, Italy
a r t i c l e
i n f o
Article history: Received 12 October 2011 Accepted 28 December 2011
Keywords: Acute inflammatory demyelinating polyneuropathy Cranial nerve palsy Conduction block Multifocal motor neuropathy
a b s t r a c t Multifocal motor neuropathy (MMN) is characterized by slowly progressive, predominantly distal, asymmetric limb weakness and partial conduction blocks (CB) of motor axons. Cranial nerve involvement and respiratory failure are uncommon. We report two patients who exhibited unilateral hypoglossal and abducens palsy as presenting signs. Other remarkable features were autonomic instability and respiratory failure due to bilateral phrenic nerve involvement. Treatment with intravenous (IV) immunoglobulin (Ig) resulted in an improvement. Patient 2, who showed IgM reactivity against ganglioside GM1, has been receiving maintenance therapy with IVIg for 7 years. We speculate that cranial weakness of our patients could be due to CB similar to those detected in the motor nerves of the extremities. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Multifocal motor neuropathy (MMN) is characterized by slowly progressive, asymmetric limb weakness, with minimal or no sensory symptoms.1,2 Diagnostic criteria include a partial conduction block (CB) of motor axons at sites that are uncommon for compression or entrapment.1,2 A CB is defined as equal or greater than 50% reduction in the compound muscle action potential (CMAP) amplitude or at least 40% reduction in area between proximal and distal stimulation in nerves with a temporal dispersion of less than 30%.1,2 Cranial nerve weakness is an uncommon presenting sign of MMN.1–5
2. Case reports 2.1. Patient 1 A 64-year-old man was admitted after a 2-month history of hand cramping, shortness of breath, and abdominal distension. On admission, he presented left-sided tongue palsy with fasciculation, without pharyngeal weakness. He was able to walk; the upper and lower extremity strength was scored 4/5 proximally, and 3/5 distally on the Medical Research Council (MRC) scale. His deep reflexes were weakened in the upper, and were absent in the lower limbs. Sensation was intact. Stool cultures excluded Campylobacter jejuni infection. Within 5 days, the weakness progressed to an asymmetric tetraparesis, with his distal strength graded between 1/5 and 2/5 in his upper and lower limbs. Anti-ganglioside GM1,1,2 anti-acetylcholine receptor antibody assays (on days 9 and 15) were negative. Respiratory insufficiency required supple⇑ Corresponding author. Tel.: +39 059 4225573; fax: 39 059 4223898. E-mail address: [email protected] (G. Galassi).
mentary oxygen therapy and monitoring in the intensive care unit (ICU). Phrenic nerve involvement was confirmed by the bilateral absence of CMAP from diaphragm muscle. Cerebrospinal fluid (CSF) examination (days 5, 7, and 23) showed normal protein content and no cells. Routine laboratory tests were unremarkable. Electrophysiology (days 5, 8, and 17) showed definite CB1,2 at the axilla–elbow, elbow–wrist, and popliteal fossa–ankle segments of the median, ulnar, and tibial nerves. F-waves were not delayed, except in the tibial nerve. Distal latencies and velocity across segments with CB were within normal limits. Sensory conduction studies of ulnar, median, and sural nerves were normal. The concentric needle electromyography (EMG) demonstrated acute and chronic partial denervation in multiple muscles. The patient declined tongue and paraspinal EMG. Intravenous immunoglobulin (IVIg, 0.4 g/kg for 5 days) was given. He exhibited progressive recovery from the 3rd week and onward, becoming able to stand unaided. Eighteen weeks after initial onset, his tongue and extremity weakness relapsed with the same intensity. An IVIg course was given monthly (0.4 g/kg for 5 days) for 6 months. Electrodiagnostic studies at 5 and 7 months confirmed CB in 6 of 8 tested motor nerves. Table 1 shows serial electrophysiological results for patient 1. Twenty eight weeks after onset, the patient was areflexic with strength scored 3/5 proximally in the upper limbs, 1/5 in the wrist extensors, intrinsic hand, and feet muscles. His clinical condition worsened due to septic shock in the 8th month of his illness. 2.2. Patient 2 A 32-year-old woman awoke with horizontal diplopia on right lateral gaze and paresthesias in the dorsal aspects of her left lower limb and right hand. No preceding illnesses were reported. Neurological evaluation revealed right-sided abducens and hypoglossal
1734
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1733–1735
Table 1 Serial electroneurography of patient 1 with hypoglossal weakness Motor nerve studyA
1 month
5 months
7 months
Normal limits in controls
Right median Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, E–W) Minimal F-wave latency (ms)
3.5 4.0/2.1 60.0 24.6
3.6 6.0/1.5 52.3 27.8
3.3 6.1/4.0 56.5 30.0
64 >4 >49 631
Right ulnar Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, BE–W) Minimal F-wave latency (ms)
3.1 7.8/2.0 56.8 27.0
3.0 6.2/3.0 54.1 28.6
2.6 7.6/1.8 52.2 29.4
64 >6 >49 631
Right tibial Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, PF–A) Minimal F-wave latency (ms)
5.8 6.0/2.1 45.7 47.9
5.2 4.0/2.0 42.2 46.7
3.5 6.3/1.5 43.7 52.9
66 >3 >46 645
Sites of CB and % changes in CMAP amplitude at diagnosis Axilla–elbow, E–W (55–57%)
Axilla–above elbow, BE–W (50–64%)
PF–A (>60%)
CB = conduction block, CMAP = compound muscle action potential, D/P = distal/proximal, E–W = elbow–wrist, BE–W = below elbow–wrist, PF–A = popliteal fossa–ankle. A Recording sites were the abductor pollicis brevis (median), abductor digiti minimi (ulnar), and abductor hallucis longus (tibial).
palsy and deep areflexia. CSF, edrophonium chloride (the Tensilon test), MRI, and her visual-evoked responses were normal. The cranial deficits fully recovered within 1 week. After 1 month, the diplopia and tongue weakness relapsed associated with 3/5 weakness in the right ulnar, left peroneal and tibial distributions. CB were detected in the axilla–elbow, elbow–wrist, and popliteal fossa–ankle segments of the right median, both ulnar, right peroneal and tibial nerves;1,2 median and ulnar sensory conductions recorded concurrently over identical nerve segments were normal. The anti-GM1 IgM titer was elevated 7 times greater than normal limits.1,2 There was no response to oral prednisone. Repeated IVIg (2 g/kg every 2 months) improved ocular, tongue, and extremity strength, which stabilized to 2/5 to 3/5 throughout. Ophthalmoplegia and tongue weakness showed exacerbations during the 7 years of follow-up. At 87 months after her first presentation, CB were found in the median, ulnar, peroneal, and tibial nerves. Table 2 shows this patient’s serial electroneurographic results; conduction velocity in the motor nerves showed minimal slowing. CMAP showed less than 30% temporal dispersion, differing from that expected in chronic inflammatory demyelinating polyneuropathy (CIDP).1,2
3. Discussion We report two patients with MMN1,2 with unilateral cranial nerve involvement as presenting signs. Neither patient had preceding infections or abnormal haematological tests. The remarkable features were relapsing weakness in arms and legs, bilateral phrenic nerve involvement, and dysautonomia in patient 1. CBs were confined to the extremity motor nerves and persisted on consecutive studies which showed a dramatic selectivity of the condition for motor axons, with normal sensory conduction identified in the same segments as the motor neuropathy.1,2 This feature differentiated the disorder from CIDP.1,2 In addition, our patients did not show the physiological consequences of demyelination commonly observed in CIDP, such as prolonged distal motor latencies, marked conduction slowing, and excessive temporal dispersion.1,2 Repeated IVIg, unlike oral prednisone, provided some benefit. Clinical remission did not correlate with the electrophysiological reversal of CB.1,2 In both patients, the needle EMG showed chronic partial denervation at multiple sites. Patient 2 showed IgM reactivity against GM1.1,2 Our initial diagnosis of Guillain Barre’ syndrome (GBS) was based on a subacute onset of cranial and oculomotor
Table 2 Serial electroneurography of patient 2 with abducens and hypoglossal weakness Motor nerve studyA
1 month
51 months
87 months
Normal limits in controls
Right median Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s E–W) Minimal F-wave latency (ms)
4.2 16.0/4.4 52.0 46.5
3.4 9.5/3.0 43.8 35.6
3.2 8.8/4.6 42.0 38.2
64 >4 >49 631
Right ulnar Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, BE–W) Minimal F-wave latency (ms)
3.2 15.6/5.0 46.7 55.2
2.8 9.6/2.9 44.6 43.0
4.1 4.0/1.0 46.6 Absent
64 >6 >49 631
Right tibial Distal latency (ms) CMAP amplitude D/P (mV) Conduction velocity (m/s, PF–A) Minimal F-wave latency (ms)
5.5 19.6/4.2 57.5 49.7
5.0 17.0/3.8 43.2 50.3
4.2 16.8/7.0 44.5 47.7
66 >3 >46 645
Sites of CB and % changes in CMAP amplitude at diagnosis Axilla–elbow, E–W (53–57%)
Axilla–above elbow, BE–W (66–70%)
PF–ankle (>60%)
CB = conduction block, CMAP = compound muscle action potential, D/P = distal/proximal, E–W = elbow–wrist, BE–W = below elbow–wrist, PF–A = popliteal fossa–ankle. A Recording sites were the abductor pollicis brevis (median), abductor digiti minimi (ulnar), and abductor hallucis longus (tibial).
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1733–1735
1735
Table 3 Reports of multifocal motor neuropathy with cranial nerve involvement Yearref
Age (years)* gender
Onset/evolution
Limb weakness distribution
Cranial nerve involvement
Antiboby/Ig isotype
Treatment
Clinical outcome
19869
38/M
Slow
Asymmetric
IX, X, XII
IgM anti-GM1
Not reported
3
1992
26/M
Slow
Asymmetric
Right XII
Normal
IVIg, steroid
19975
45/M
Acute in 8–10 days
Asymmetric
Not evaluated
Steroid, cyclophosphamide, PE
20017
46/M
Slow
Asymmetric
Bilateral VI and VII, left IV, XI, XII Bilateral III, IX, X
8
72/M
Slow
Asymmetric
Right XII
IgG, IgM antiGM1, anti-MAG IgM anti-GM1
IVIg, cyclophosphamide, PE, steroids,azathioprine IVIg
Quadriplegia, death (21 years) Improvement over 5 months Improvement over 15 months Quadriplegia, death (18 years) Improvement over 3 months
2002
*
Age at first symptom, F = female, GM1 = ganglioside GM1, IVIg = intravenous immunoglobulin, M = male, PE = plasma exchange.
weakness, respiratory failure, and autonomic dysfunction (patient 1). CSF examinations were normal. Involvement of the cranial motor or mixed nerves, such as the oculomotor, vagal, and hypoglossal nerves, is found in 26% to 61% of demyelinating GBS6; asymmetric cranial nerve palsy, if persistent (except for the facial nerve), is considered indicative of diagnoses other than GBS.4,6–9 In our patients, the diagnosis of GBS was challenged when the disease recurred greater than 3 times without full recovery in between.1,2 Ozaki et al.10 reported a 16-year-old boy with asymmetric weakness, abducens palsy, and a high titer of anti-GM1 antibodies; electrophysiology showed decreased velocity, CB, and temporal dispersion in motor and sensory axons, which fulfilled the diagnostic criteria of CIDP.1,2,10 Involvement of cranial nerves in MMN has been reported as initial sign only by two authors:5,8 ophthalmoplegia was the presenting symptom of Pringle case who subsequently developed multiple cranial nerve palsies.5 Hypoglossal neuropathy was the presenting sign of Axelsson’s patient8 and of another with Lewiss-Sumner syndrome masquerading as MND.4 Bulbar and diaphragm weakness were observed after 20 years of progressive disease;9 a patient of Kaji et al.3 developed hand and foot weakness followed by reversible tongue hemiatrophy several months later. Beydoun et al.7 reported bilateral ptosis and autonomic instability before death in a patient with secondary amyloidosis (Table 3). Cranial nerves are generally spared in MMN; bulbar involvement or cranial weakness are exclusion clinical criteria for MMN.1 However, the diagnosis of MMN should be considered when cranial weakness persists or relapses in association with multifocal CB. Cranial weakness could be due to chronic CB, similar to findings in the extremity motor nerves.5,8 The correct diagnosis doi:http://dx.doi.org/10.1016/j.jocn.2011.12.030
in such patients has clinical implications for treatment as well as for prognosis. Acknowledgements We thank Drs. K. Funakoshi and M. Odaka for the antiganglioside antibody assays performed at the Department of Neurology, Dokkyo University, Japan, in one of the patients reported. References 1. Van Schaik IN, Bouche P, Illa I, et al. European Federation of Neurological Societies/Peripheral nerve societies guidelines on management of multifocal motor neuropathy. Eur J Neurol 2006;13:802–8. 2. Chaundhry V, Corse AM, Cornblath DR, et al. Multifocal motor neuropathy: electrodiagnostic features. Muscle Nerve 1994;17:198–205. 3. Kaji R, Shibasaki H, Kimura J. Multifocal demyelinating motor neuropathy:cranial nerve involvement and immunoglobulin therapy. Neurology 1992;42:506–9. 4. Weiss MD, Oakley JC, Meekins GD. Hypoglossal neuropathy in Lewis-Sumner syndrome masquerading as motor neuron disease. Neurology 2006;67:175–6. 5. Pringle CE, Belden J, Veitch JE, et al. Multifocal motor neuropathy presenting as ophthalmoplegia. Muscle Nerve 1997;20:347–51. 6. Sakakibara Y, Mori M, Kuwabara S, et al. Unilateral cranial and phrenic nerve involvement in axonal Guillain-Barre’ syndrome. Muscle Nerve 2002;25:297–9. 7. Beydoun SR, Rison RA, Commins D. Secondary amyloidosis as a life ending event in multifocal motor neuropathy. Muscle Nerve 2001;24:1396–402. 8. Axelsson G, Leidholm LJ. Multifocal motor neuropathy-unusual cause of hypoglossal palsy. Lakartidningen 2002;99:1448–50. 9. Roth G, Rohr J, Magistris MR, et al. Motor neuropathy with proximal multifocal persistent conduction block, fasciculations and myokymia. Eur Neurol 1986;25:416–23. 10. Ozaki I, Baba M, Kurihara A, et al. Chronic inflammatory demyelinating polyneuropathy (CIDP) with ophthalmoplegia: a case with asymmetric limb weakness and high titers of anti-GM1 antibody. Eur J Neurol 1996;3:457–61.