Too much, too soon?

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  • LETTERS TO THE EDITOR

    PARASPINAL MYOPATHY WITH NOVELSHARD-LIKE COMPACT AGGREGATES OFTHIN FILAMENTS

    An 83-year-old woman developed dropped head and pos-terior neck pain over 6 weeks while denying other neu-rological symptoms. Neurological examination showedisolated mild weakness of neck extensor muscles butwas otherwise normal. Magnetic resonance imaging ofthe cervical spine was normal, electrophysiological studieswere consistent with a myopathic process isolated to theneck extensors, and creatine kinase was 80 IU/L. A diag-nosis of isolated neck extensor myopathy was made. Myas-thenia gravis (MG) was ruled out by physical examinationand negative anti-acetylcholine receptor antibodies, andamyotrophic lateral sclerosis (ALS) was ruled out withphysical examination and electrophysiological studies.

    Paraspinal muscle biopsy showed rare interstitial mono-nuclear inammation, groups of atrophic bers and inter-nalized myonuclei (Fig. 1A), and scattered rimmed vacuoles(Fig. 1B), reminiscent of inclusion-body myositis (IBM).Sections treated with Congo red stain highlighted sarcoplas-mic inclusions. On ultrastructural examination there werecompact, elliptical inclusions comprised of thin, 4-nm-diam-eter laments with periodicity (Fig. 1C and D) lacking cross-linkage. No intranuclear inclusions were found.

    Over the next year she was stable and was treatedonly with a neck brace and analgesics.

    Numerous conditions are associated with droppedhead syndrome. The majority of cases occur in ALS andMG. Approximately 2% of ALS patients13 and 3% ofMG4 patients have head drop as the initial disease mani-festation. Head drop as the primary manifestation ofmyopathy is rarer. Although it can be part of the clinicalspectrum of adult-onset nemaline myopathy,5 carnitinedeciency,6,7 and adult acid maltase deciency,8 it is usu-ally accompanied by generalized weakness. A literaturereview yielded 4 cases of IBM with isolated head drop.912

    All had a consistent clinical phenotype of an elderly per-son with relatively normal creatine kinase whose headdrop was unresponsive to treatment. The skeletal musclehistology often included brosis, atrophy, and variablenumbers of rimmed vacuoles. When electron microscopywas undertaken, unlike our case, typical intranuclear la-mentous inclusions of IBM were found.

    The paraspinal muscles are uncommonly biopsied,but two small studies suggested their normal histologycan include type I predominance, type II atrophy,ragged red bers, and myonecrosis.13,14

    No reports of normal or diseased paraspinal muscleshave described inclusions resembling those seen in this case.Despite their reactivity for Congo red stain, the ultrastruc-ture of these inclusions diverges from amyloid, as they havea shard-like arrangement and a smaller diameter (4-nm la-ment vs. the 7.510-nm amyloid lament). They bear someresemblance to Hirano bodies, which have been describedrarely in skeletal muscle,15 but these laments are thinnerand lack cross-bridging and actin immunopositivity.

    In conclusion, our case of an elderly woman with iso-lated neck extensor myopathy and light-microscopic fea-tures of IBM demonstrated unique sarcoplasmic inclu-sions on ultrastructural examination, which we havetermed shard-like compact aggregates of thin la-ments. In recognition of the paucity of investigationinto this uncommonly biopsied muscle, it is possible thatthese inclusions are a normal or possibly age-relateddegenerative nding of the paraspinal muscles, or a hith-erto undescribed form of isolated paraspinal myopathy.

    Julia Lee Keith, MD, FRCPC1

    Lorne Zinman, MS, MD, FRCPC, MSc2

    Sandra Cohen, RT3

    Beverly Young, MLT, BAS1

    Juan Bilbao, MD, FRCPC1

    1Department of Anatomical Pathology, Sunnybrook HealthSciences Centre, University of Toronto, Toronto, Ontario, Canada

    2Department of Internal Medicine, Division of Neurology,Sunnybrook Health Sciences Centre, University of Toronto,Toronto, Ontario, Canada

    3Electron Microscopy, St. Michaels Hospital, University ofToronto, Toronto, Ontario, Canada

    1. Katz JS, Wolfe GI, Burns DK, Bryan WW, Fleckenstein JL, Barohn RJ.Isolated neck extensor myopathy: a common cause of dropped headsyndrome. Neurology 1996;46:917921.

    2. Grob D, Brunner NG, Namba T. The natural course of myastheniagravis and effect of therapeutic measures. Ann NY Acad Sci 1981;377:652669.

    3. Jokelainen M. Amyotrophic lateral sclerosis in Finland. Acta NeurolScand 1977;56:194204.

    4. Wolfe GI, Bank WJ. Pseudokyphosis in motor neuron disease cor-rected by the pocket sign [abstract]. Muscle Nerve 1994;17:1091.

    5. Lomen-Hoerth C, Simmons ML, Dearmond SJ, Layzer RB. Adultonset nemaline myopathy: another cause of dropped head. MuscleNerve 1999;22:11461150.VC 2011 Wiley Periodicals, Inc.

    Letters to the Editor MUSCLE & NERVE July 2011 145

  • 6. Karpati G, Carpenter S, Engel AG. The syndrome of systemic carni-tine deciency: clinical, morphologic, biochemical, and pathophysio-logic features. Neurology 1975;25:1624.

    7. Vandyke DH, Griggs RC, Markesbery W, Dimauro S. Hereditary car-nitine deciency of muscle. Neurology 1975;25:154159.

    8. Trend PJ, Wiles CM, Spencer GT, Morgan-Hughes JA, Lake BD, Pat-rick AD. Acid maltase deciency in adults: diagnosis and manage-ment in ve cases. Brain 1985;108:845860.

    9. Luque FA, Rosenkilde CE, Valsamis M, Danon MJ. Inclusion bodymyositis presenting as the dropped head syndrome. Brain Pathol1994;4:568.

    10. Hund E, Heckl R, Goebel HH, Menck HM. Inclusion body myositispresenting as isolated erector spinae paresis. Neurology 1995;45:993994.

    11. Oerlemans WGH, de Visser H. Dropped head syndrome and bent spinesyndrome: two separate clinical entities or different manifestations ofaxial myopathy? J Neurol Neurosurg Psychiatry 1998;65:258259.

    12. Suarez GA, Kelly JJ. The dropped head syndrome. Neurology 1992;42:16251627.

    13. Wharton SB, Chan KK, Pickard JD. Paravertebral muscles in disease ofthe cervical spine. J Neurol Neurosurg Psychiatry 1996;61:461465.

    14. Laroche M, Delisle MB, Aziza R, Lagarrigue J, Mazieres B. Is campto-cormia a primary muscular disease? Spine 1995;20:10111016.

    15. Fernandez R et al. Adult glycogenosis II with paracrystalline mito-chondrial inclusions and Hirano bodies in skeletal muscle. Neuro-muscul Disord 1999;9:136143.

    Published online 15 June 2011 in Wiley Online Library(wileyonlinelibrary.com). DOI 10.1002/mus.22093

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    MYASTHENIA GRAVIS EXACERBATIONAFTER CETIRIZINE ADMINISTRATION

    A 22-year-old woman presented with a 6-month historyof proximal muscle weakness, dysphagia, and weaknessof jaw closure in December 1992. Neurological exami-nation revealed nasal speech, weakness of proximalmuscles of upper and lower limbs (4/5), and bilateralBell sign. Ptosis and diplopia were apparent after afatigability test. The serum acetylcholine receptorbinding antibody titer was elevated. Repetitive nervestimulation at 3 HZ with recording from abductor dig-iti minimi and nasalis induced decremental responsesof 18% and 31%, respectively. Chest tomographyshowed both enlarged and small nodular lesions with-out contrast enhancement in the thymus gland. Thepatient had symptomatic improvement in response totreatment with pyridostigmine (60 mg every 8 h) overthe next 10 days. At the time of discharge, she wasasymptomatic. The thymus gland was removed 20 dayslater and was found to have follicular hyperplasia.This patient would be classied as IIIb according tothe Myasthenia Gravis Foundation of America (MGFA)clinical classication. The patient was in complete

    FIGURE 1. (A) Hematoxylin and eosinstained section (original magnification 4) showing groups of atrophic fibers and myopathicabnormalities with foci of mononuclear inflammation (inset, original magnification 10). (B) Rimmed vacuoles on modified Gomori tri-chrome stain (original magnification 40). (C, D) Ultrastructural examination yielded novel shard-like compact aggregates of thin, 4-nmfilaments with periodicity (indicated by arrows). [Color figure can be viewed in the online issue, which is available at

    wileyonlinelibrary.com.]

    146 Letters to the Editor MUSCLE & NERVE July 2011

  • stable remission (CSR) according to the MGFA post-intervention status for the next 18 years of follow-up.In May 2010 she was treated with cetirizine 10 mg/dayfor allergic sinusitis (AS), which had been present for7 days. No other medications were added. Within 24hours of the initial dose, she developed diplopia, fa-cial weakness, nasal voice, dysphagia, and weakness ofjaw closure. Cetirizine was discontinued at 48 h, andher symptoms improved progressively over the next 2days. Five days after starting cetirizine the patient hadminimal manifestations, and pyridostigmine wasrestarted. She became asymptomatic 10 days later. Thepyridostigmine was discontinued 3 weeks later, with nosubsequent exacerbation of MG.

    A wide variety of drugs have been associated withclinical deterioration of MG.1 Antihistamines are struc-turally similar to histamine, and mainly they are competi-tive blockers of histamine receptors.2 Cetirizine, a non-sedating, second-generation H1 receptor antagonist, hasa relative incidence of adverse anticholinergic and cen-tral nervous system effects similar to that produced byplacebo.3 Our patient developed ocularfacialbulbarsymptoms within the rst 24 hours after starting cetiri-zine. The main argument implicating cetirizine in thedeterioration of MG is the time interval between admin-istration and onset of symptoms, which coincides withthe drugs time to peak plasma concentration (around 1hour). Furthermore, this hypothesis is supported by theprompt recovery after withdrawal of the drug (steady-state plasma levels were reached by the second day) andthe absence of other medications added.4 The AS is lesslikely to have been the cause of the MG exacerbation,because no deterioration of MG was documented duringthe 7 days from clinical onset to the start of cetirizine.We are unaware of other reports of deterioration of MGafter administration of antihistamines. We believe thatantihistamines, especially cetirizine, may be detrimentalin patients with MG, and they should only be adminis-tered with caution in patients known to have thisdisease.

    Alvaro Cobo Calvo, MD1

    Maria Anto`nia Albert Aguilo, MD1

    Carlos Casasnovas Pons, MD, PhD1,2

    1Neuromuscular Unit, Neurology Department

    2Centro de Investigacion Biomedica en Red de EnfermedadesNeurodegenerativas IDIBELL, Hospital Universitari de Bellvitge,LHospitalet de Llobregat, Barcelona, Spain

    1. Eric TW. Drugs and myasthenia gravis, an update. Arch Intern Med1997;157:399408.

    2. Pearlman DS. Antihistamines: pharmacology and clinical use. Drugs1976;12:258273.

    3. Simons FE. New H1 receptor antagonist: clinical pharmacology. ClinExp Allergy 1990;20(suppl 2):1924.

    4. Molimard M, Diquet B, Benedetti MS. Comparison of pharmacoki-netics and metabolism of desloratadine, fexofenadine, levocetirizineand mizolastine in humans. Fundam Clin Pharmacol 2004;18:399411.

    Published online 15 June 2011 in Wiley Online Library(wileyonlinelibrary.com). DOI 10.1002/mus.22096

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    DEMYELINATING SYMMETRIC MOTORPOLYNEUROPATHY WITH HIGH ANTI-GM1ANTIBODY TITER: DO WE NEED TO SPLIT?

    Multifocal motor neuropathy (MMN) is characterized bystepwise or progressive muscle weakness with wasting andfasciculations.14 Characteristic features include a ndingindicative of demyelination, motor conduction block(CB) outside of sites of nerve compression.4 Although CBremains the hallmark of MMN, it was not consideredessential for diagnosis.5 OFerrall et al. reported a patientwith progressive motor demyelinating neuropathy associ-ated with elevated titers of antibodies against the ganglio-side GM1.6 The patient had mostly distal weakness andnormal sensory examination; over 5 years, his disorderremained symmetric and conned to the motor system.Treatment with intravenous immunoglobulins (IVIg),oral prednisone, methylprednisolone, and cyclophospha-mide had questionable benet. The patient6 had demyeli-nating features in the motor nerves, including prolongeddistal latencies, conduction slowing, prominent temporaldispersion, and CBs.14 The investigators6 concluded thatthe extent of ndings was far beyond those expected fromreported series of MMN patients.15 The electrophysiolog-ical abnormalities spared the sensory bers, which demon-strated selectivity of this condition for motor axons anddifferentiated it from chronic inammatory demyelinat-ing polyneuropathy (CIDP).4,5 The patients serum con-tained elevated titers of IgM antibodies to GM1.

    Among a cohort of 29 MMN patients followed at ourinstitution since 1993, we identied 4 males affected byrelentless disease that began in both hands and progressedsymmetrically to the lower limbs. The age of onset wasbetween 25 and 50 years. The proximal power in upperand lower extremities remained almost intact over 1517years, whereas distal muscle strength (hand grip, ngerextension, and foot dorsiexion) was graded 12/5 on theMedical Research Council scale after 813 years of illness.Sensation to light touch, pin-prick, and vibration was intact,but deep tendon reexes were diminished throughout. Allpatients had anti-GM1 antibody titers 5060 times greaterthan the mean value of controls on enzyme-linked immu-nosorbent assay.3 Spinal uid examination was normal.Genetic testing for peripheral myelin protein 22 or P0mutations was negative. On serial electrophysiology, CBswere found in at least three motor nerves, and there wereprolonged distal latencies and delayed or absent F-waves.14

    Reduced distal CMAP amplitudes observed during diseaseprogression were related to axon loss.14,7 All patientsreceived IVIg (0.41.0 g/kg body weight) every 68 weeks.

    We agree with OFerrall et al.6 that their patient didnot demonstrate clinically what is usually expected inMMN.15 However, the motor conduction abnormalitiesin their patient were asymmetric from initial presenta-tion; in addition, his gait was unsteady, which can beseen in MMN.3 Twenty-two percent of the patientsreported by Taylor et al.7 exhibited a symmetrical neu-ropathy, and 4 of the patients observed by Kinsellaet al.8 had a symmetric lower motor neuron disorderand high-titer anti-GM1 antibodies. Kimura et al.9

    reported 5 patients with motor-dominant relapsingremitting CIDP with predominant upper limb weakness;

    Letters to the Editor MUSCLE & NERVE July 2011 147

  • none had detectable autoantibodies in serum, as did thevan der Berg-Vos et al.10 patients, who had a multifocalinammatory demyelinating neuropathy with features incommon with MMN and CIDP.

    The pathogenesis of MMN remains largely elusive;sera from a substantial subgroup of patients contain IgMantibodies against GM1, which is abundantly expressedin motor axons and Schwann cell surfaces.13,5,11 Catset al.3 studied a large cohort of MMN patients and con-cluded that anti-GM1 IgM antibody screening is themost efcient diagnostic marker. Patients with anti-GM1IgM antibodies had lower Medical Resea...