LETTERS TO THE EDITOR
ACUTE ATAXIC SENSORY NEURONOPATHY RESULTING FROM PODOPHYLLlN INTOXICATION We describe an acute toxic sensory neuronopathy that occurred in association with podophyllin ingestion. A 33-year-old woman ingested 300 mL of an extract from 15 gm of dried rhizome and roots of Podophyllum peltaturn, containing approximately 500 mg of podophyllin resin, for relief of postpartum abdominal fullness. Thirty minutes later, she developed headache followed by nausea, vomiting, and watery diarrhea. Two days later, rapidly spreading numbness involving both arms and legs resulted in severe ataxia. Examination on day 7 after ingestion revealed profound loss of proprioception and vibration sense below the knees and elbows with minimal hypoestehsia. She had normal muscle strength, but was arefiexic with flexor plantar responses bilaterally. Marked dysmetria and incoordination further worsened with eye-closing. She had no orthostatic hypotension o r other autonomic dysfunction. Normal studies on admission included routine clinical laboratory test and analysis of cerebrospinal fluid. A follow-up examination 9 months later revealed loss of vibration sense only to the level of the wrist and ankle, restored position sense, and normal gait despite persistent areflexia. O n day 9, conduction studies showed reduced sensory action potentials of ulnar (5.5 pV), median (2.0 FV) and sural nerve (15.0 pV) with normal motor responses. On day 2 1 , a repeat study revealed further reduction in sural response (7.5 pV) with absent ulnar and median nerves sensory potentials. Stimulation of the median o r tibial nerve failed to elicit the H reflex. T h e electromyography of extensor digitorum brevis and abductor hallucis was normal. Stimulation of the ulnar nerve evoked no somatosensory evoked potentials (SSEPs) at Erb's point, neck, o r scalp. Sequential median and posterior tibial nerve SSEPs showed progressive abnormalities as illustrated in Figure 1. To summarize, the clinical findings consisted of severe kinesthestic disability despite the preservation of strength, with gait ataxia, areflexia, and rapidly deterio-
Letters to the Editor
rating position sense, i.e., features characteristic of ataxic sensory n e ~ r o n o p a t h y .SSEPs3 ~ and sequential nerve conduction studies' localized the lesion to the dorsal root ganglia, with absence of sensory evoked potentials and a well-preserved motor response. If only peripheral nerves were involved, some degree of motor dysfunction would be expected and the central nervous system evoked potentials could be preserved even in the absence of peripheral sensory evoked responses as the result of central amplification.* T h e unique combination of absent H reflexes with preservation of normal motor and sensory nerve conduction initially suggested the conduction abnormality along the reflex pathway between the dorsal root and the ventral horn. The subsequent diminution and disappearance of sensory responses implied progression of the disease to involve the dorsal root ganglia or sensory nerve more distally. Based on these electrodiagnostic characteristics, we postulate that our patient has a sensory neuronopathy despite the lack o f pathological confirmation. Ming-Hong Chang, MD Kong-Pin Lin, MD Lin-An Wu, MD Kwong-Kum Lao, MD Neurological Center Veterans General Hospital-Taipei Taipei, Taiwan, R.O.C.
1 . Donofrio DD, Alessi AG, Albers JW, Knapp RH, Blaivas M: Electrodiagnostic evolution of carcinomatous sensory neuronopathy. M w c l e Nerue 1989;12:508-513. 2. Eisen A, Purves S, Hoirch M: Central nervous system amplification: its potential in the diagnosis of' early multiple sclerosis. Neurology 1982;32:359-364. 3 . Malinow K, Yannakdkis GD, Glusman SM, et al: Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjogren's syndrome. Ann Nrurol 1986;20:335337. 4. Windehank A J , Blexrud MD, Dyck PJ, Dauhe JR, Karnes JL: T h e syndrome of acute sensory neuropathy: Clinical features anti electrophysiologic anti pathologic changes. NeuroloLgy 1990;40:584-591.
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2 1 s t day
9 t h day
Median SSEPs
Median SSEPs 23.8(N19) C4 ’ -Fz 17.6 “13) 31.2 (P22) m2-F~
10.2 (N9)
10.2 (N9) 0
E r b ’ s-Fz
P o s t e r i o r tibia1 SSEPs
P o s t e r i o r t i b i a l SSEPs
77.8 (N45) 67.0 (N45) 0
--
0
68.6(P37)
54.6(P37)
T12-rostr.
3cm vert.
9.0
9.0
PF-Ed.
kn.
T
I 1.0 *v
0.5 U V
FIGURE 1. Evolution of median and posterior tibial SSEPs. Median nerves SSEPs show a selective conduction delay or block between N9 (Erb’s point) and N13 (cervical cord). Posterior tibial nerve SSEPs reveal markedly prolonged peak latency and decreased amplitude of P37, worse on the 21st day. T12-rostr. 3 cm vert.: T12 spinous process-rostra1 3cm vertebral body; PF-med. kn.: popliteal fossa-medial knee joint
514
Letters to the Editor
MUSCLE 8. NERVE
ADril 1992
A NEW INSTRUMENT FOR OBTAINING TISSUE BIOPSY OF MUSCLE In a letter to the Journal,2 Dr. Irwin M. Siegel wrote about a new clamp for muscle biopsies to prevent contraction artifacts.' He had used the clamp in 60 muscle biopsies to his entire satisfaction. We have used a very similar instrument in more than 100 muscle biopsies during the last 3 years, also with optimal results (Fig. 1). T h e only difference between our clamp and the one used by D. Siegel being the angulation at the grasping end. We completely agree with Dr. Siegel's excellent impression about this kind of clamps that allows a one-hand operation and helps to obtain a better muscle sample.
Dr. Marco A. Sosa, MD Depto. de Neurologia Marcoleta 387 Pontificia Universidad Catolica, de Chile Santiago, Chile
DORSAL NERVE OF THE PENIS NERVE CONDUCTION VELOCITY: A NEW TECHNIQUE: A REPLY Regarding Drs. Clawson and Cardenas' article on dorsal nerve of the penis conduction velocity.' Since they demonstrated that the distal latency of this nerve does not change with the amount of tension on the penis, why bother with a traction device and clamps? Why not just obtain the distal latency without penile traction, and then at the end of the procedure, have the patient or the physician apply brief traction for the measurement of distance, for use in calculating velocity? This would seem equally reliable and more comfortable.
Len Weber, MD West Dodge Neurologic Clinic Omaha, Nebraska 68132 1. Clawson DR, Cardenas DD: Dorsal nerve of the penis nerve conduction velocity: A new technique. 1991; 14:845-849.
DORSAL NERVE OF THE PENIS NERVE CONDUCTION VELOCITY: A NEW TECHNIQUE: A REPLY
FIGURE 1. Clamp for muscle biopsies.
Carper,ter s, Karpati c;: po~huluaof Skeletal Mu,,clP, N~~ York, Churchill Livingstone, 1984. 2. Siegel I: A new instrument for obtaining tissue biopsy of musle. Muscle N e w ? 3991;14:85.
We feel that there is less room for error with placing the penis in a traction device and then subsequently placing the electrodes. This is similar to doing a nerve conduction study across the elbow and initially placing the elbow in 90" of flexion to remove redundancy of the nerve while doing the study, and then measuring the distance in that position. As well, when doing this study on the penis one finds that the skin is extremely loose and any traction and movement of the penis and electrodes post stimulation may result in an inaccurate measurement. The other benefit of this traction device is that it stabilizes the penis in a certain position, making the technique easier. Without the splint, the penis tends to be somewhat of a dynamic organ, and it does not always maintain a constant position. David R. Clawson, MD Northwest Hospital 1530 North 115th Seattle, Washington 98133
A NEW INSTRUMENT FOR OBTAINING TISSUE BIOPSY OF MUSCLE: A REPLY I am pleased that Dr. Soza has had success using a muscle biopsy clamp with a design similar to mine. I have found that the angulation at the grasping end allows easier access to the biopsy site, provides better visualization during the procedure, and facilitates muscle dissection with the tips of the clamp. We are currently preparing to fabricate the instrument in plastic. It will then be disposable and less expensive. Irwin M. Siegel, MD Rush-Presbyterian-St. Luke's Medical Center Chicago, Illinois 60640
Letters to the Editor
MYOTONIA IN PATIENTS TREATED FOR CANCER WITH DlDEMNlN B The search for new agents effective against malignancy has produced many compounds with novel mechanisms of action. Myotonic discharges developed in 7 patients treated with didemnin B, a recently discovered tunicate peptide containing the amino acid iso-statine. The didemnins are 3 depsipeptides (Fig. 1) derived from the sea squirt, a Caribbean tunicate of the family Didemnidae, genus Trididemnum, of which didemnin-B (Fig. 1) has the most potent antiviral, antitumor, and cytotoxic
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CH3 0
u
0 Me+
Thr
Pro
DlDEMNlN A ,
Leu
R=H
9
DlDEMNlN 8, R:CHsCHOHC-N
FI
-
FI cTc
DlDEMNlN C, R=CHsCHOHC-
FIGURE 1. Chemical structures of didemnins A, Sta, isostaine.
B, and C. iso-
activity.’ The mechanisms of action of the didemnins are not fully known, but inhibition of protein synthesis and to a lesser extent inhibition of DNA synthesis have been noted e ~ p e r i m e n t a l l y . ~ ~ ~ Twenty three patients with advanced carcinoma of the lung or breast were treated with didemnin-B (dose 6.3 mgs/m2 to 7.6 mgs/m2 monthly) as a phase one
study and underwent routine prospective and follow-up electromyographic (EMG) study as part of their evaluation. Patients received as many as 3 courses of this therapy. Nine patients had lung cancer and 14 breast cancer with all but one of the lung cancer patients being men and all the breast cancer patients women. The patient’s ages ranged from 33 to 73 years with a mean age of 52. Prior chemotherapy was used in all patients consisting of combinations of cisplatin, cyclophosphamide, vinblastine, 5-fluorouracil, and doxirubicin. Seven patients developed myotonic discharges consisting of trains of repetitive single-phase positive sharp waves with varying amplitude and frequency. None of these patients developed clinical myopathic disease although 2 of the 23 patients studied developed symptomatic myopathy without having myotonia (Tables 1 and 2). Among the patients with lung cancer, following their second course of didemnin B, 3 patients developed mild axonal neuropathies and 1 developed a lumbosacral radiculopathy secondary to tumor as well as a mild generalized axonal neuropathy. One patient who had previously demonstrated a sensory neuropathy showed essentially normal EMG and nerve conduction studies. Another patient (patient no. 5) developed symptomatic myopathy characterized by elevated creat-
Table 1. Patient summaries Patient No.
AgeISex
Diagnosis
Dose
Neuromuscular symptoms
48 M 60 M 57 M 33 M 54 M 61 F 62 F
Non small cell lung carcinoma Non small cell lung carcinoma Non small cell lung carcinoma Non small cell lung carcinoma Non small cell lung carcinoma Small cell lung carcinoma Adenocarcinoma of breast Adenocarcinoma of breast Adenocarcinoma of breast
6.3, 6.3 6.3 6.3, 6.3 6.3, 6.3 6.3, 7.6 6.3 6.3
Severe weakness Moderate weakness Moderate weakness Moderate weakness Severe weakness Severe weakness None Severe weakness None
71 F 60 F
6.3, 7.6, 6.3 6.3
Table 2. Patient findings. ~~ ~~~~
Patient No
9
516
Electromyography Myotonia Myotonia Myotonia Myotonia Myopathy Myotonidmyopathy Myotonia Myopathy with fibrillations and positive sharp waves Myotonidmyopathy
Letters to the Editor
Transaminase
t
LDH
CPK
Aldolase
Comments
t
nd nl
t t
nl nl
nl nl
nl nl
nl nl
Malignant pericardial effusion Died tumor advance Died tumor advance Died tumor advance Biopsy necrosis without inflammation Biopsy necrosis without inflammation Advancing tumor myotonia resolved Remission symptoms resolved on lower dose
nl
nl
t
nd
Rapidly advancing systemic disease
nl nl nl
nl
nl nl nl nl
t 1‘
t t
t t
nl
t
nl nl
MUSCLE & NERVE
April 1992
ine phosphokinase (CPK) and aldolase, but had no evidence o f myotonia. This patient had been using illicit intravenous drugs during the course of his treatment which was stopped due to disease progression. A deltoid muscle biopsy demonstrated multifocal necrosis with regeneration of muscle fibers and moderately severe type I1 fiber atrophy. All 5 remaining lung cancer patients developed myotonic discharges in the medial gastrocnemius muscles without having evidence of clinical myotonia. Only 1 of these patients had myopathic symptoms (patient No. 6 in the Tables), but her disease course was complicated by rapidly advancing oat cell lung cancer, concurrent steroid therapy, and preexisting diabetes mellitus with evidence of a sensorimotor neuropathy on admission to the protocol. Because this patient had elevated CPK, lactic dehydrogenase (LDH), transaminase, and aldolase levels as well as proximal weakness, she underwent a muscle biopsy, which demonstrated necrotic and regenerating fibers and type I1 fiber atrophy without inflammatory infiltrates. She was unable to sit u p due to profound proximal weakness toward the end of her illness and died from tumor progression. In the other 4 lung cancer patients with myotonia, electrolyte, aldolase, and CPK levels were within normal limits. One patient (patient No. 1) had generalized weakness and elevated transaminases and LDH believed to be due to his systemic disease, which included malignant pericarditis. None of these patients had symptoms of myotonia or myopathy. Generalized weakness was a common complaint in the patients with lung cancer, likely reflecting their advanced disease and the rigors of treatment. We can only speculate about why these patients developed myotonic discharges while receiving didemnin B for the treatment of advanced carcinoma. T h e myotonia did not appear to be dose related, frequently occurring after administration of the first dose, but insufficient numbers of patients were studied to be certain of this. As didemnin-B has a unique mechanism of action and potential as a chemotherapy agent, further study is warranted to elucidate the means by which it affects muslces. Arthur D. Forman, MD Dong M. Shin, MD Robert Jackson, BS University of Texas M.D. Anderson Cancer Center 1515 Holcombe Blvd. Houston, Texas 77030
Chun HG, Davies B, Hoth D, et al: Didemnin B: The first marine compound entering clinical trials as an antineoplastic agent. Invest New Drugs 1986;4:279-284. Dorr FA, Kuhn JG, Phillips J , Van Hoff DD: Phase 1 clinical and pharmacokinetic investigation of didemnin B a cyclic depsipeptide. Eur J Cancer Clzn Oncol 1988;ll: 12251231. Hossian MB, Van Der Helm D, Autel J, Sheldrick GM,
Letters to the Editor
Sandvja SK, Weinheimer AJ: Crystal and molecular structure of didemnin-B an antiviral and cytotoxic depsipeptide. Pro6 Natl Acad Sci USA 1988;85:4118-4122.
CALF ENLARGEMENT, S l RADICULOPATHY, AND FOCAL MYOSITIS* In 1986, a 40-year-old man underwent lumbosacral laminectomy. This relieved his low back and right buttock pain, but caused persistent numbness in the right S1 distribution. He began to notice progressive swelling of the right calf in December 1988. The right calf felt tight and achy, especially when standing. He occasionally had cramps in the hamstrings and calf. Otherwise, he had no complaints. An examination in August 1990 showed only enlargement and tenderness of the right calf, and an absent right ankle jerk. Routine chemistry and sedimentdtion rate were normal. Serum CK was mildly elevated (450 U/L). There was no eosinophilia. Biopsy of the right gastrocnemius showed increased variability in fiber diameter, with both hypertrophic and atrophic fibers. Internal nuclei were increased, and there was some fiber splitting. Chronic inflammatory infiltrates were noted, in one instance involving a vessel (Fig. 1A). Necrotic muscle fibers were present, isolated and in small groups. In many instances, fiber necrosis was associated with an inflammatory infiltrate consisting primarily of eosinophils (Fig. 1B). An NADH-TR reductase-stained section demonstrated fiber type grouping. Electrodiagnostic studies were performed 2 months after the biopsy. Nerve conduction studies were normal except for borderline delay of the right tibia1 F-wave. EMG showed complex repetitive discharges and large motor unit potentials with decreased recruitment in the right gastrocnemius. A similar pattern without spontaneous activity was found in the right biceps femoris. Other right lower extremity muscles were normal. Prednisone was prescribed at an initial dose of 30 mg daily and tapered off over about 6 weeks. T h e patient’s pain and swelling decreased during prednisone treatment, but these symptoms recurred after it was discontinued. He underwent radiation therapy between January 22 and February 6, 1991. This consisted of 2,400 RADs to the calf in 12 fractions. When seen again in March 1991, his pain and calf enlargement had significantly lessened. Calf enlargement in patients with S1 radiculopathy typically develops gradually, months to years after symptoms of radiculopathy begin.3s4EMG shows evi-
*Presented at the annual meeting of the American Association of Electrodiagnostic Medicine, Vancouver, Canada, September 1991.
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are sufficiently bothersome and an inflammatory process is documented. David A. Krendel, MD Department of Neurology Emory University School of Medicine 1365 Clifton Road, N.E. Atlanta, Georgia 30322 Ellis V. Hedaya, MD Atlanta Neurological Clinic Atlanta, Georgia Alan J. Gottleib, MD Atlanta, Georgia I . Heffner RR, Uarron SA: Denervating changes in focal myositis, a benign inflammatory pseudotumor. Arch Pathol I.nh Med 1980; 104:261-264. 2. Letlerrnan RJ, Salanga V D , Wilbourn AJ, Hanson M K , Dudley AW: Focal inflammatory myopathy. Mu.sclr N ~ J P 1984;7:142- 146. 3. Montagna l’, Martirielli P, Rasi F, Cirignotta F, Govoni E, Lugaresi F.: Muscular hypertrophy after chronic radiculopathy. Arch Neul-i~l1984;41:397- 398. 4. Ricker K, Kohkamm R, Moxley RT: Hypertrophy of the calf with S-1 radiculopathy. A d Nrul-ol 1988;45:660-664.
FIGURE 1. (A) A chronic inflammatory infiltrate involving a small intramuscular vessel. (Frozen tissue, H & E. Bar = 50 (L.) (6) Necrotic muscle fibers contain and are surrounded by inflammatory cells, many of which are eosinophils (arrows). (Paraffin embedded tissue, H & E. Bar = 25 (L.)
dence of denervation, often with conlplex repetitive discharges in the enlarged g a s t r ~ c n e m i u sSome .~ biopsies have shown hypertrophy of many individual fibers,3 but others have shown increased endomysial connective tissue (p~eudohypertrophy).~ Our findings suggest that a secondary inflammatory process may occasionally occur in denervated muscle. Denervated calf muscles may be predisposed to damage during walking, which might cause a secondary inflammatory process. Enlargement could then occur because of edema and eventual fibrosis. T h e eosinophils might indicate an autoimmune response to damaged muscle fibers. This could be analogous to a condition that Heffner and Barron’ called “benign inflammatory pseudotumor.” They found coexisting inflammatory myopathy and evidence of chronic denervation in enlarged muscles. Lederman and co-workers‘ found clinical evidence suggesting nerve involvement in their 3 patients with focal inflammatory myopathy, one of whom had enlargement of the involved muscle. Calf enlargement with S 1 radiculopathy usually does not cause disability, but our patient illustrates that local radiation therapy can be helpful when symptoms
518
Letters to the Editor
DYSTROPHIN IS LOCALIZED TO THE PLASMA MEMBRANE OF HUMAN SKELETAL MUSCLE FIBERS BY ELECTRON=MICROSCOPIC CYTOCHEMICAL STUDY I have followed the exchanges between Drs. Wakayama, Carpenter, and Karpati 011 the topic of dystrophin and its localization in skeletal muscle. I am surprised that so little serious comment has been made on the suitability of immunocytochemistry applied to ultrathin sections of skeletal muscle as a technique to study the localization of dystrophin. Neither Wakayama nor Carpenter and Karpati referred to the definitive study on the localization of dystrophin by Cullen et al.3 who used a monoclonal antibody to the rod domain of dystrophin and immunogold labelling (used first in this type of work by Watkins et a15) to show that the roddomain was localized beneath the plasma membrane of the muscle fibre. Apart from the clarity o f the images produced by immunogold labeling, an additional advantage of immunogold labeling is that it is possible to quantitate the distribution and localization of the protein. T h e use of other specific monoclonal antibodies to defined regions of dystrophin will make it possible to study the localization of various regions of the protein. Such refinement is not possible with the relatively crude technique of immunocytochemistry. John B. Harris PhD Regional Neurosciences Centre Newcastle General Hospital Newcastle upon Tyne NE4 6BE England 1. Carpenter S, Karpati G, Zubrzycka-Gaarn, et al: Dystrophin is localized to the plasma membrane of human skeletal
MUSCLE & NERVE
April 1992
muscle fibers by electron-microscopic cytochemical study. Mzwcle Nerve 1990;13:376-380. Carpenter S, Karpati G : Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electron-microscopic cytochemical study: A reply (letter). MzLrcle Nerve 1991;14:577. Cullen MJ, Walsh J, Nicholson LV, Harris JB: Ultrastructural localization of dystrophin in human muscle by using gold immunolabelling. Proc Roy Sac Lond (Biol) 1990; 240: 197-2 10. Wakayama Y : Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electronmicroscopic cytochemical study (letter). Muscle Nerve 1991; 14:576-577. Watkins S, Hoffman EP, Slayter HS, Kunkel LM: Immunoelectron microscopic localization of dystrophin in myofibres. Nature (London) 1988;333:863-866.
DYSTROPHIN IS LOCALIZED TO THE PLASMA MEMBRANE OF HUMAN SKELETAL MUSCLE FIBERS BY ELECTRON=MICROSCOPIC CYTOCHEMICAL STUDY=A REPLY Although the aim of my letter' was not to include all the references dealing with dystrophin localization, I regret that I did not cite the important article of Cullen et al.' I agree that localization of dystrophin to the inner side of the skeletal muscle plasma membrane can be demonstrated with greater clarity with the use of immunogold-labeled antibodies at the ultrastructural level. In addition, quantitation data are potentially available. However, the immunoperoxidase technique can also provide an accurate localization of the dystrophin molecule in this setting.
Yoshihiro Wakayama, MD, PhD Division of Neurology Department of Medicine Showa University Fujigaoka Hospital Yokohama, 227 Japan 1. Cullen MJ, Walsh J , Nicholson LVB, Harris JB: Ultrastructural localization of dystrophin in human muscle by using gold irnniunolabelling. Proc Roy Soc Lond (Biol) 1990;240: 197-2 10. 2. Wakayama Y: Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electronmicroscopic cytochemical study. Muscle Newe 1991;14576577.
POLYGLUCOSAN BODY DISEASE In their article, Cafferty et all presented 2 patients who had clinical signs which they claimed were peculiar to polyglucosan body disease. T h e patients were older than 50 and had both peripheral neuropathy and myelopathy with urinary incontinence. T h e authors discussed that polyglucosan body found in the sural nerve biopsies of their patients wasn't specific for the disease which has been reported in only 15 patients. In fact
Letters to the Editor
polyglucosan body can be found in other diseases and in healthy subjects. Dementia was present in 8 of 15 cases of polyglucosan body disease reported in the literature. Symptoms began in the fifth or sixth decade and continued for 3 to 20 years.5 Vitamin B,, deficiency is manifested in the peripheral nervous system by the signs and symptoms of neuropathy and in the central nervous system by myelopathy, optic atro hy, and dementia.3 Optic atrophy is rare. Chanarin estimated an incidence of 0.3% in patients with this disease. Contrary to the opinion of Cafferty et al, the toristellation of peripheral nerve and central disorders with sphincter problems should first suggest subacute combined degeneration of the spinal cord due to vitamin B,, deficiency. T h e disease usually progresses over several weeks or months; however, it may be rapid or may be more chronic, developing over a year or more. Electrophysiological studies indicate the neuropathy to be secondary to a dying-back type of axonal degeneration. Neuropathological studies have demonstrated loss of large myelinated fibers in distal sensory nerves as well as axonal degeneration in individually teased fiber preparation^.^ Hematological findings such as megaloblastic anemia is not a must in subacute combined degeneration of the spinal cord.3 The determination of serum vitamin B,, level is essential in the diagnosis of the treatable condition of vitamin B deficiency. T h e diagnosis of polyglucosan body disease, which has similar neurologic and neurophysiologic properties, could only then be considered.
f '
Musa Onar, MD Department of Neurology Ondokuz Mayis University Medical Faculty 55139 Samsun, Turkey. 1 . Cafferty MS, Lovelace RE, Hays AP, et al: Polyglucosan body disease. Muscle Nerve 1991;14:102- 106. 2 . Chanarin I: Pernicious anemia and other vitamin B,, deficiency states. Abstr World Med 1970;44:73. 3 . Davies-Jones GAB: Neurologic manifestations of hematological disorders, in Aminoff MJ (ed): Neurology and Crnerul Medicine. New York, Churchill Livingstone, 1989, pp 188. 4. Fine EJ, Soria E, Pdroski MW et al: The neurophysiological profile of vitamin B,, deficiency. Muscle Nerve 1990;13: 152- 164. 5. Gray F, Gherardi R, Marshall A, et al: Polyglucosan body disease. ,I Neuroputh Exp Neurol 1988;40:459-474.
POLYGLUCOSAN BODY DISEASE: A REPLY Dr. Musa Onor's comments on the similarity of the manifestation of B 12 deficiency and polyglucosan disease are important. B,, deficiency should be entertained in the differential diagnosis of patients presenting with the constellation of dementia, myelopathy, and neuropathy as described in our article.
MUSCLE & NERVE
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In current times HIV should also be routinely tested on these patients. Maureen S. Cafferty, MD Department of Medicine Neurology Division St. Luke's/Roosevelt Hospital Center 114th Street & Amsterdam Avenue New York, N.Y. 10025 Robert E. Lovelace, MD Arthur B. Hays, MD Serenella Surides, MD Salvatore Di Mauro, MD Lewis P. Rowland, MD Neurological Institute College of Physicians and Surgeons Columbia University New York, N.Y. 10032
CONDUCTION BLOCK IN HEREDITARY MOTORANDSENSORYNEUROPATHY TYPE I Conduction block has been encountered in several acquired neuropathies during the past decade and is a
A Wrist
0.2 ms
characteristic feature of some of these.',' Although the concept of conduction block is receiving increasing attention, several problems attached to its assessment seem to remain underemphasized. First, there is no agreement about its electrophysioSecond, it may be hazardous to logical definition. apply the criteria used to define conduction block in acute demyelinating neuropathies to chronic disorders because in the latter partial denervation is frequently present. A third problem, i.e., attaining supramaximal stimulation, was experienced by us investigating patients with hereditary motor and sensory neuropathy type I (HMSN I). We studied 37 patients, aged 4 to 67 years, from six families with autosonial dorninantly inherited HMSN I . CMAPs were recorded from the abductor pollicis brevis muscle after percutaneous stimulation of the median nerve at the wrist and at the elbow with rectangular pulses of 0.1 ms duration and a maximuni amperage of 80 mA. T h e electrodes, the anode being held proximally along the nerve, were carefully placed at the optimal site. Surface forearm temperature was 3 2 - 34" C. Conduction block was considered to be present if
'.'.'
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0.2 ms . 5.4mV
.
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'
.
.
.
.
.
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.
.
.
- 40mA -
60.rn A
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.
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-
. .
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. .
. .
. .
.
.
80mA '
I
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.
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.
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.
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.
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.
FIGURE 1. Compound muscle action potentials recorded from the abductor pollicis brevis muscle after stimulation of the median nerve at the wrist and at the elbow in two patients (A and B) with HMSN I. Note the differences in calibration.
520
Letters to the Editor
MUSCLE 8, NERVE
April 1992
the proportional CMAP amplitude decrease on proximal as compared with distal stimulation was at least 50%, provided that the proportional increase in CMAP duration was 15% o r less. Nine individuals (25%) met these criteria, four of them showing CMAP amplitude reductions of more than 80%. However, supramaximal stimulation may not have been attained. Therefore, three individuals were reexamined using longer stimulus durations. In one, conduction block appeared to be absent with supramaximal stimulation of 0.2 ms duration. In another, conduction block may o r may not have been present, since strong stimuli lasting 0.2 ms were too painful to allow supramaximal stimulation (Fig. IA). In the third subject, conduction block was present on supramaximal stimulation lasting 0.3 ms (Fig. lb). Our data show that differentially decreased nerve excitability may quite easily cause an electrodiagnostic artifact mimiciking conduction block and emphasize the necessity of longer-duration, often painful stimuli in HMSN I, and probably also in other disorders. This has implications for the usefulness of conduction block in the distinction between acquired and inherited demyelinating polyneuropathies as proposed by Lewis and Sumner.' This distinction may indeed be difficult at times, especially if no family data are available to confirm heredity. In support of the findings of O h and Chang,3 our observations indicate that caution should be exercised in using conduction block as a diagnostic tool. T h e occurrence of a large CMAP amplitude reduction on proximal stimulation, irrespective of whether this represents true of "false" conduction block, does not preclude the possibility of HMSN 1. These patients should be tested for the presence of the duplication in chromosome 1 7 ~ 1 1 . 2which , we recently demonstrated to be most likely a mutation responsible for HMSN Ia."
Jessica E. Hoogendijk, MD* Marianne de Visser, MD, PhD* Lo J. Bout, PhD* Frans G.I. Jennekens, MD, PhDt Bram W. Ongerboer, MD, PhD* *Department of Neurology Academic Medical Center 1105 AZ Amsterdam The Netherlands tDepartment of Neurology Academic Hospital Utrecht Utrecht The Netherlands 1. Brown WF, Feasby TE: Conduction block and denervation in Guillain- Barre polyneuropathy. Brain 1984;107:219239. 2. Lewis RA, Sumner AJ: T h e electrodiagnostic distinction between chronic familial and acquired demyelinative neuropathies. Neurology 1982;32:592- 596. 3. O h SJ, Chang CW: Conduction block and dispersion in hereditary motor and sensory neuropathy. Muscle Nerve, 1987;10:656A. 4. Pestronk A , Chaudhry V, Feldman EL, Griffin J W , Cornblath DR, Denys EH, et al. Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnor-
Letters to the Editor
malities, and high titers of aritiglycolipide antibodies. Ann Neurol 1900;27:316-326. 5. Raeymaekers P, Timmerman V, E Nelis, De Jonghe P, J E Hoogendijik, F Baas, et al. Duplication in Charcot-MarieToorh neuropathy type la(CMT1a) Neuromusc Disord 1991;1:93-97.
CONDUCTION BLOCK IN HEREDITARY MOTOR SENSORY NEUROPATHY, TYPE I: CASE REPORT Supramaximal stimulation is the most important technical parameter required for an adequate motor nerve conduction study.' Supramaximal stimulation should be achieved by adjustment of the stimulus duration as well as its intensity. Stimulus parameters should not be limited to the certain parameters as Hoogendijk et a1 did in the initial test.' In HMSN type I, for example, a stimulus duration longer than 0.1 ms is needed in a majority of cases, as observed by these authors in the later test. T h e following case report illustrates this technical point and presents the core message in our study." A 32-year-old white man had difficulty running and had had a high arched foot since childhood. The diagnosis of HMSN Type I was made in his grandmother, father, and son. He had had progressive weakness in the legs for the previous 2 years. Examination showed 3-0 MRC strength in the anterior tibialis and gastrocnemius muscles, pes cavus, diffuse atrophy in the lower leg, thick peroneal nerves at the fibular head, and sensory impairment below the mid-shin level. The s u r d nerve biopsy showed prominent "onion-bulb formation." The nerve conduction study showed no response in the peroneal and posterior tibia1 nerves with the maximal stimulation parameters available on the EMG machine (0.5 msi99 mA). In the median and ulnar nerves, the motor nerve conduction velocity showed uniform slowing between the segments as well as between the nerves (Fig. 1). In the median nerve, conduction block (48% to 61% decrease) was observed in the wrist-elbow segment by the peak-to-peak and negative-amplitude, and negative- and total-area methods. In the ulnar nerve, conduction block (45% to 60% decrease) was observed in the above elbow and axilla segment by all four methods. These values were clearly outside the normal 2 S.D.2 In this case, supramaximal stimulation mean was achieved with a stimulus duration of 0.5 ms and stimulus intensity of 65 to 87 mA. These data indicate that a conduction block exists over the wrist-elbow segment in the median and the above elbow-axilla segment in the ulnar nerves by the best available practical method (area method). This case illustrates several points: (1) supramaxima1 stimulation should be achieved by the adjustment of stimulus duration and intensity. T h e limitation should be the maximum available duration and intensity of a given EMG machine; and (2) conduction block exists even in the presence of uniform nerve conduc-
+
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521
tion slowing. Conduction block is not necessarily indicative of “focal” demyelination, but could well be an expression of diffuse demyelination over that segment. Differentiation between the two mechanisms should be studied by short-segment stimulation technique. ‘1’0 guarantee adequacy, our study was done prospectively. We found conduction block in 28% of cases when the data from the median and ulnar nerves were analyzed following Lewis’s method.“ Case B in Hoodgendijks sLudy confirms the finding in our abstract.
T h e core message of our abstract is that differentiation between HMSN type 1 and chronic inflammatory demyelinating polyneuropathy (CIDP) is not possible with the nerve conduction study alone in a substantial number of cases.
Shin J. Oh, MD Department of Neurology
The University of Alabama at Birmingham, UAB Station Birmingham, Alabama 35294
Median Nerve Latency PP-amplitude NP-amplitude N-duration T-duration N-area T-alYa
NP-amplitude N-duration T-duration N-area T-area
15.10 3.73 2.01 7.70 19.10 7.65 16.10
NCV
14.20
NCV PP-amplitude
r&
w
630 8.00 5.19 7.30 21.60 14.80 3750
-53.4 % -61.3 % +5.4 % -11.6% ‘ -48.3 % -57.190
Ulnar Nerve Latency
6.20
NCV
14.8
BE
AE Ax
NCV PP-amplitude NP-amplitude N-duration T-duration N-area T-area
20.70 5.74 333 9.50 32.20 12.70 30.70
NCV PP-amplitude NPamplitude N-duration T-duration N-area T-area
15.64 2.96 138 10.50 29.00 6.95 16.50
-48.4 % -59.79% clO.0 % -9.9 % -45.2 % -46.3 %
FIGURE 1. Conduction block in the wrist (W)-elbow (E) segment in median nerve and in the above elbow (AE)-axilla (Ax) segment in the ulnar nerve. Various electrophysiological data are listed to the right of figures. Latency represents the terminal latency by msec; NCV, nerve conduction velocity by rneterisec; PP-amplitude, peak-to-peak amplitude (L2-L4) by mV; NP-amplitude, negative-peak arnplitude (L1-L2) by mV; N-duration, duration of negative wave (L1-L3) by rnsec; T-duration, duration of total wave (LVL5); N-area, area of the negative wave (Ll-L2-L3) by rnV/msec; and T-area, area of the negative and positive waves (L1-L2-L3-L4-L5). Percentages represent the difference between the repreproximal and distal CMAPs in the segment of conduction block in the various parameters. sents an increase and -, a decrease.
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522
Letters to the Editor
MUSCLE &
NERVE
April 1992
1. Hoogendijk J E , de Visser M, Bour IJ, Jennkens FGI, Origerboer BW: Conduction block in hereditary motor and sensory neuropathy type I. Mu.scle Nervc 1992;15:520-521. 2. Kim ED, Kuruoglou HR, O h SJ: What is the best diagnostic index of conduction block and temporal dispersion? Muscle Ncme 1991; 14:884. 3 . Lewis RA, Sumner A]: T h e electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies. Neurology 1982;32:592-596. 4. Oh SJ: Clinical Electromyography: Nerve Conduction Studies. Baltimore, University Park Press. 1984. 5. Oh SJ, Chang CW: Conduction block and dispersion in hereditary motor and sensory neuropathy. Muscle Nerve 1987;10:656A.
CONDUCTION BLOCK I N HEREDITARY MOTORANDSENSORYNEUROPATHY TYPE I: A REPLY I appreciate the opportunity to respond to letters commenting upon the electrophysiologic criteria for distinguishing between acquired and hereditary chronic demyelinating neuropathies advanced by Dr. Richard Lewis and me some 9 years ago.:! It is gratifying that these criteria have received such general acceptance over the past decade. It is also not surprising that they might require some modification after this length of time. T h e two letters draw attention to the presence of “conduction block” in some cases of HMSN 1. I d o not accept that these are examples of bonefide conduction block. It is now widely recognized that a drop in ampli-
Letters to the Editor
tude and area of the distal to proximal CMAP responses is occasionally encountered in motor conduction studies of nerves associated with advanced chronic denervation from whatever cause, because of the problems created by positive- negative interphase cancellation of the few remaining large polyphasic motorunit potentials. Under these conditions conduction block can only be established if it is clearly restricted to localized nerve segments, or if by identifying all individual recruitable motorunits it can proven that their summed responses cannot reconstitute the distally evoked CMAP. I would also like to remind readers that the presence or absence of conduction block is not the most important of the criteria to use in clinical practice in distinguishing the chronic hereditary from chronic idiopathic demyelinating polyneuropathy (CIDP). It is the remarkable uniformity of the conduction slowing along all segments of all peripheral myelinated axons that so characterizes the electrophysiologic abnormality of HMSN 1 . By contrast CIDP usually shows multifocal or segmental conduction changes. Austin J. Sumner, MD Department of Neurology LSU Medical Center 1542 Tulane Avenue New Orleans, Louisiana 70112
’
1. Cornblath DR, Sumner AJ, Daube J et al: Conduction block in clinical practice. Muscle Nerve 1991;14:809-871. 2. Lewis RA, Sumner AJ: T h e electrodiagnostic distinction between chronic familial and acquired demyelinative neuropathies. Neuroloa 1982;32:592-597.
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ACUTE ATAXIC SENSORY NEURONOPATHY RESULTING FROM PODOPHYLLlN INTOXICATION We describe an acute toxic sensory neuronopathy that occurred in association with podophyllin ingestion. A 33-year-old woman ingested 300 mL of an extract from 15 gm of dried rhizome and roots of Podophyllum peltaturn, containing approximately 500 mg of podophyllin resin, for relief of postpartum abdominal fullness. Thirty minutes later, she developed headache followed by nausea, vomiting, and watery diarrhea. Two days later, rapidly spreading numbness involving both arms and legs resulted in severe ataxia. Examination on day 7 after ingestion revealed profound loss of proprioception and vibration sense below the knees and elbows with minimal hypoestehsia. She had normal muscle strength, but was arefiexic with flexor plantar responses bilaterally. Marked dysmetria and incoordination further worsened with eye-closing. She had no orthostatic hypotension o r other autonomic dysfunction. Normal studies on admission included routine clinical laboratory test and analysis of cerebrospinal fluid. A follow-up examination 9 months later revealed loss of vibration sense only to the level of the wrist and ankle, restored position sense, and normal gait despite persistent areflexia. O n day 9, conduction studies showed reduced sensory action potentials of ulnar (5.5 pV), median (2.0 FV) and sural nerve (15.0 pV) with normal motor responses. On day 2 1 , a repeat study revealed further reduction in sural response (7.5 pV) with absent ulnar and median nerves sensory potentials. Stimulation of the median o r tibial nerve failed to elicit the H reflex. T h e electromyography of extensor digitorum brevis and abductor hallucis was normal. Stimulation of the ulnar nerve evoked no somatosensory evoked potentials (SSEPs) at Erb's point, neck, o r scalp. Sequential median and posterior tibial nerve SSEPs showed progressive abnormalities as illustrated in Figure 1. To summarize, the clinical findings consisted of severe kinesthestic disability despite the preservation of strength, with gait ataxia, areflexia, and rapidly deterio-
Letters to the Editor
rating position sense, i.e., features characteristic of ataxic sensory n e ~ r o n o p a t h y .SSEPs3 ~ and sequential nerve conduction studies' localized the lesion to the dorsal root ganglia, with absence of sensory evoked potentials and a well-preserved motor response. If only peripheral nerves were involved, some degree of motor dysfunction would be expected and the central nervous system evoked potentials could be preserved even in the absence of peripheral sensory evoked responses as the result of central amplification.* T h e unique combination of absent H reflexes with preservation of normal motor and sensory nerve conduction initially suggested the conduction abnormality along the reflex pathway between the dorsal root and the ventral horn. The subsequent diminution and disappearance of sensory responses implied progression of the disease to involve the dorsal root ganglia or sensory nerve more distally. Based on these electrodiagnostic characteristics, we postulate that our patient has a sensory neuronopathy despite the lack o f pathological confirmation. Ming-Hong Chang, MD Kong-Pin Lin, MD Lin-An Wu, MD Kwong-Kum Lao, MD Neurological Center Veterans General Hospital-Taipei Taipei, Taiwan, R.O.C.
1 . Donofrio DD, Alessi AG, Albers JW, Knapp RH, Blaivas M: Electrodiagnostic evolution of carcinomatous sensory neuronopathy. M w c l e Nerue 1989;12:508-513. 2. Eisen A, Purves S, Hoirch M: Central nervous system amplification: its potential in the diagnosis of' early multiple sclerosis. Neurology 1982;32:359-364. 3 . Malinow K, Yannakdkis GD, Glusman SM, et al: Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjogren's syndrome. Ann Nrurol 1986;20:335337. 4. Windehank A J , Blexrud MD, Dyck PJ, Dauhe JR, Karnes JL: T h e syndrome of acute sensory neuropathy: Clinical features anti electrophysiologic anti pathologic changes. NeuroloLgy 1990;40:584-591.
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2 1 s t day
9 t h day
Median SSEPs
Median SSEPs 23.8(N19) C4 ’ -Fz 17.6 “13) 31.2 (P22) m2-F~
10.2 (N9)
10.2 (N9) 0
E r b ’ s-Fz
P o s t e r i o r tibia1 SSEPs
P o s t e r i o r t i b i a l SSEPs
77.8 (N45) 67.0 (N45) 0
--
0
68.6(P37)
54.6(P37)
T12-rostr.
3cm vert.
9.0
9.0
PF-Ed.
kn.
T
I 1.0 *v
0.5 U V
FIGURE 1. Evolution of median and posterior tibial SSEPs. Median nerves SSEPs show a selective conduction delay or block between N9 (Erb’s point) and N13 (cervical cord). Posterior tibial nerve SSEPs reveal markedly prolonged peak latency and decreased amplitude of P37, worse on the 21st day. T12-rostr. 3 cm vert.: T12 spinous process-rostra1 3cm vertebral body; PF-med. kn.: popliteal fossa-medial knee joint
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Letters to the Editor
MUSCLE 8. NERVE
ADril 1992
A NEW INSTRUMENT FOR OBTAINING TISSUE BIOPSY OF MUSCLE In a letter to the Journal,2 Dr. Irwin M. Siegel wrote about a new clamp for muscle biopsies to prevent contraction artifacts.' He had used the clamp in 60 muscle biopsies to his entire satisfaction. We have used a very similar instrument in more than 100 muscle biopsies during the last 3 years, also with optimal results (Fig. 1). T h e only difference between our clamp and the one used by D. Siegel being the angulation at the grasping end. We completely agree with Dr. Siegel's excellent impression about this kind of clamps that allows a one-hand operation and helps to obtain a better muscle sample.
Dr. Marco A. Sosa, MD Depto. de Neurologia Marcoleta 387 Pontificia Universidad Catolica, de Chile Santiago, Chile
DORSAL NERVE OF THE PENIS NERVE CONDUCTION VELOCITY: A NEW TECHNIQUE: A REPLY Regarding Drs. Clawson and Cardenas' article on dorsal nerve of the penis conduction velocity.' Since they demonstrated that the distal latency of this nerve does not change with the amount of tension on the penis, why bother with a traction device and clamps? Why not just obtain the distal latency without penile traction, and then at the end of the procedure, have the patient or the physician apply brief traction for the measurement of distance, for use in calculating velocity? This would seem equally reliable and more comfortable.
Len Weber, MD West Dodge Neurologic Clinic Omaha, Nebraska 68132 1. Clawson DR, Cardenas DD: Dorsal nerve of the penis nerve conduction velocity: A new technique. 1991; 14:845-849.
DORSAL NERVE OF THE PENIS NERVE CONDUCTION VELOCITY: A NEW TECHNIQUE: A REPLY
FIGURE 1. Clamp for muscle biopsies.
Carper,ter s, Karpati c;: po~huluaof Skeletal Mu,,clP, N~~ York, Churchill Livingstone, 1984. 2. Siegel I: A new instrument for obtaining tissue biopsy of musle. Muscle N e w ? 3991;14:85.
We feel that there is less room for error with placing the penis in a traction device and then subsequently placing the electrodes. This is similar to doing a nerve conduction study across the elbow and initially placing the elbow in 90" of flexion to remove redundancy of the nerve while doing the study, and then measuring the distance in that position. As well, when doing this study on the penis one finds that the skin is extremely loose and any traction and movement of the penis and electrodes post stimulation may result in an inaccurate measurement. The other benefit of this traction device is that it stabilizes the penis in a certain position, making the technique easier. Without the splint, the penis tends to be somewhat of a dynamic organ, and it does not always maintain a constant position. David R. Clawson, MD Northwest Hospital 1530 North 115th Seattle, Washington 98133
A NEW INSTRUMENT FOR OBTAINING TISSUE BIOPSY OF MUSCLE: A REPLY I am pleased that Dr. Soza has had success using a muscle biopsy clamp with a design similar to mine. I have found that the angulation at the grasping end allows easier access to the biopsy site, provides better visualization during the procedure, and facilitates muscle dissection with the tips of the clamp. We are currently preparing to fabricate the instrument in plastic. It will then be disposable and less expensive. Irwin M. Siegel, MD Rush-Presbyterian-St. Luke's Medical Center Chicago, Illinois 60640
Letters to the Editor
MYOTONIA IN PATIENTS TREATED FOR CANCER WITH DlDEMNlN B The search for new agents effective against malignancy has produced many compounds with novel mechanisms of action. Myotonic discharges developed in 7 patients treated with didemnin B, a recently discovered tunicate peptide containing the amino acid iso-statine. The didemnins are 3 depsipeptides (Fig. 1) derived from the sea squirt, a Caribbean tunicate of the family Didemnidae, genus Trididemnum, of which didemnin-B (Fig. 1) has the most potent antiviral, antitumor, and cytotoxic
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CH3 0
u
0 Me+
Thr
Pro
DlDEMNlN A ,
Leu
R=H
9
DlDEMNlN 8, R:CHsCHOHC-N
FI
-
FI cTc
DlDEMNlN C, R=CHsCHOHC-
FIGURE 1. Chemical structures of didemnins A, Sta, isostaine.
B, and C. iso-
activity.’ The mechanisms of action of the didemnins are not fully known, but inhibition of protein synthesis and to a lesser extent inhibition of DNA synthesis have been noted e ~ p e r i m e n t a l l y . ~ ~ ~ Twenty three patients with advanced carcinoma of the lung or breast were treated with didemnin-B (dose 6.3 mgs/m2 to 7.6 mgs/m2 monthly) as a phase one
study and underwent routine prospective and follow-up electromyographic (EMG) study as part of their evaluation. Patients received as many as 3 courses of this therapy. Nine patients had lung cancer and 14 breast cancer with all but one of the lung cancer patients being men and all the breast cancer patients women. The patient’s ages ranged from 33 to 73 years with a mean age of 52. Prior chemotherapy was used in all patients consisting of combinations of cisplatin, cyclophosphamide, vinblastine, 5-fluorouracil, and doxirubicin. Seven patients developed myotonic discharges consisting of trains of repetitive single-phase positive sharp waves with varying amplitude and frequency. None of these patients developed clinical myopathic disease although 2 of the 23 patients studied developed symptomatic myopathy without having myotonia (Tables 1 and 2). Among the patients with lung cancer, following their second course of didemnin B, 3 patients developed mild axonal neuropathies and 1 developed a lumbosacral radiculopathy secondary to tumor as well as a mild generalized axonal neuropathy. One patient who had previously demonstrated a sensory neuropathy showed essentially normal EMG and nerve conduction studies. Another patient (patient no. 5) developed symptomatic myopathy characterized by elevated creat-
Table 1. Patient summaries Patient No.
AgeISex
Diagnosis
Dose
Neuromuscular symptoms
48 M 60 M 57 M 33 M 54 M 61 F 62 F
Non small cell lung carcinoma Non small cell lung carcinoma Non small cell lung carcinoma Non small cell lung carcinoma Non small cell lung carcinoma Small cell lung carcinoma Adenocarcinoma of breast Adenocarcinoma of breast Adenocarcinoma of breast
6.3, 6.3 6.3 6.3, 6.3 6.3, 6.3 6.3, 7.6 6.3 6.3
Severe weakness Moderate weakness Moderate weakness Moderate weakness Severe weakness Severe weakness None Severe weakness None
71 F 60 F
6.3, 7.6, 6.3 6.3
Table 2. Patient findings. ~~ ~~~~
Patient No
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516
Electromyography Myotonia Myotonia Myotonia Myotonia Myopathy Myotonidmyopathy Myotonia Myopathy with fibrillations and positive sharp waves Myotonidmyopathy
Letters to the Editor
Transaminase
t
LDH
CPK
Aldolase
Comments
t
nd nl
t t
nl nl
nl nl
nl nl
nl nl
Malignant pericardial effusion Died tumor advance Died tumor advance Died tumor advance Biopsy necrosis without inflammation Biopsy necrosis without inflammation Advancing tumor myotonia resolved Remission symptoms resolved on lower dose
nl
nl
t
nd
Rapidly advancing systemic disease
nl nl nl
nl
nl nl nl nl
t 1‘
t t
t t
nl
t
nl nl
MUSCLE & NERVE
April 1992
ine phosphokinase (CPK) and aldolase, but had no evidence o f myotonia. This patient had been using illicit intravenous drugs during the course of his treatment which was stopped due to disease progression. A deltoid muscle biopsy demonstrated multifocal necrosis with regeneration of muscle fibers and moderately severe type I1 fiber atrophy. All 5 remaining lung cancer patients developed myotonic discharges in the medial gastrocnemius muscles without having evidence of clinical myotonia. Only 1 of these patients had myopathic symptoms (patient No. 6 in the Tables), but her disease course was complicated by rapidly advancing oat cell lung cancer, concurrent steroid therapy, and preexisting diabetes mellitus with evidence of a sensorimotor neuropathy on admission to the protocol. Because this patient had elevated CPK, lactic dehydrogenase (LDH), transaminase, and aldolase levels as well as proximal weakness, she underwent a muscle biopsy, which demonstrated necrotic and regenerating fibers and type I1 fiber atrophy without inflammatory infiltrates. She was unable to sit u p due to profound proximal weakness toward the end of her illness and died from tumor progression. In the other 4 lung cancer patients with myotonia, electrolyte, aldolase, and CPK levels were within normal limits. One patient (patient No. 1) had generalized weakness and elevated transaminases and LDH believed to be due to his systemic disease, which included malignant pericarditis. None of these patients had symptoms of myotonia or myopathy. Generalized weakness was a common complaint in the patients with lung cancer, likely reflecting their advanced disease and the rigors of treatment. We can only speculate about why these patients developed myotonic discharges while receiving didemnin B for the treatment of advanced carcinoma. T h e myotonia did not appear to be dose related, frequently occurring after administration of the first dose, but insufficient numbers of patients were studied to be certain of this. As didemnin-B has a unique mechanism of action and potential as a chemotherapy agent, further study is warranted to elucidate the means by which it affects muslces. Arthur D. Forman, MD Dong M. Shin, MD Robert Jackson, BS University of Texas M.D. Anderson Cancer Center 1515 Holcombe Blvd. Houston, Texas 77030
Chun HG, Davies B, Hoth D, et al: Didemnin B: The first marine compound entering clinical trials as an antineoplastic agent. Invest New Drugs 1986;4:279-284. Dorr FA, Kuhn JG, Phillips J , Van Hoff DD: Phase 1 clinical and pharmacokinetic investigation of didemnin B a cyclic depsipeptide. Eur J Cancer Clzn Oncol 1988;ll: 12251231. Hossian MB, Van Der Helm D, Autel J, Sheldrick GM,
Letters to the Editor
Sandvja SK, Weinheimer AJ: Crystal and molecular structure of didemnin-B an antiviral and cytotoxic depsipeptide. Pro6 Natl Acad Sci USA 1988;85:4118-4122.
CALF ENLARGEMENT, S l RADICULOPATHY, AND FOCAL MYOSITIS* In 1986, a 40-year-old man underwent lumbosacral laminectomy. This relieved his low back and right buttock pain, but caused persistent numbness in the right S1 distribution. He began to notice progressive swelling of the right calf in December 1988. The right calf felt tight and achy, especially when standing. He occasionally had cramps in the hamstrings and calf. Otherwise, he had no complaints. An examination in August 1990 showed only enlargement and tenderness of the right calf, and an absent right ankle jerk. Routine chemistry and sedimentdtion rate were normal. Serum CK was mildly elevated (450 U/L). There was no eosinophilia. Biopsy of the right gastrocnemius showed increased variability in fiber diameter, with both hypertrophic and atrophic fibers. Internal nuclei were increased, and there was some fiber splitting. Chronic inflammatory infiltrates were noted, in one instance involving a vessel (Fig. 1A). Necrotic muscle fibers were present, isolated and in small groups. In many instances, fiber necrosis was associated with an inflammatory infiltrate consisting primarily of eosinophils (Fig. 1B). An NADH-TR reductase-stained section demonstrated fiber type grouping. Electrodiagnostic studies were performed 2 months after the biopsy. Nerve conduction studies were normal except for borderline delay of the right tibia1 F-wave. EMG showed complex repetitive discharges and large motor unit potentials with decreased recruitment in the right gastrocnemius. A similar pattern without spontaneous activity was found in the right biceps femoris. Other right lower extremity muscles were normal. Prednisone was prescribed at an initial dose of 30 mg daily and tapered off over about 6 weeks. T h e patient’s pain and swelling decreased during prednisone treatment, but these symptoms recurred after it was discontinued. He underwent radiation therapy between January 22 and February 6, 1991. This consisted of 2,400 RADs to the calf in 12 fractions. When seen again in March 1991, his pain and calf enlargement had significantly lessened. Calf enlargement in patients with S1 radiculopathy typically develops gradually, months to years after symptoms of radiculopathy begin.3s4EMG shows evi-
*Presented at the annual meeting of the American Association of Electrodiagnostic Medicine, Vancouver, Canada, September 1991.
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are sufficiently bothersome and an inflammatory process is documented. David A. Krendel, MD Department of Neurology Emory University School of Medicine 1365 Clifton Road, N.E. Atlanta, Georgia 30322 Ellis V. Hedaya, MD Atlanta Neurological Clinic Atlanta, Georgia Alan J. Gottleib, MD Atlanta, Georgia I . Heffner RR, Uarron SA: Denervating changes in focal myositis, a benign inflammatory pseudotumor. Arch Pathol I.nh Med 1980; 104:261-264. 2. Letlerrnan RJ, Salanga V D , Wilbourn AJ, Hanson M K , Dudley AW: Focal inflammatory myopathy. Mu.sclr N ~ J P 1984;7:142- 146. 3. Montagna l’, Martirielli P, Rasi F, Cirignotta F, Govoni E, Lugaresi F.: Muscular hypertrophy after chronic radiculopathy. Arch Neul-i~l1984;41:397- 398. 4. Ricker K, Kohkamm R, Moxley RT: Hypertrophy of the calf with S-1 radiculopathy. A d Nrul-ol 1988;45:660-664.
FIGURE 1. (A) A chronic inflammatory infiltrate involving a small intramuscular vessel. (Frozen tissue, H & E. Bar = 50 (L.) (6) Necrotic muscle fibers contain and are surrounded by inflammatory cells, many of which are eosinophils (arrows). (Paraffin embedded tissue, H & E. Bar = 25 (L.)
dence of denervation, often with conlplex repetitive discharges in the enlarged g a s t r ~ c n e m i u sSome .~ biopsies have shown hypertrophy of many individual fibers,3 but others have shown increased endomysial connective tissue (p~eudohypertrophy).~ Our findings suggest that a secondary inflammatory process may occasionally occur in denervated muscle. Denervated calf muscles may be predisposed to damage during walking, which might cause a secondary inflammatory process. Enlargement could then occur because of edema and eventual fibrosis. T h e eosinophils might indicate an autoimmune response to damaged muscle fibers. This could be analogous to a condition that Heffner and Barron’ called “benign inflammatory pseudotumor.” They found coexisting inflammatory myopathy and evidence of chronic denervation in enlarged muscles. Lederman and co-workers‘ found clinical evidence suggesting nerve involvement in their 3 patients with focal inflammatory myopathy, one of whom had enlargement of the involved muscle. Calf enlargement with S 1 radiculopathy usually does not cause disability, but our patient illustrates that local radiation therapy can be helpful when symptoms
518
Letters to the Editor
DYSTROPHIN IS LOCALIZED TO THE PLASMA MEMBRANE OF HUMAN SKELETAL MUSCLE FIBERS BY ELECTRON=MICROSCOPIC CYTOCHEMICAL STUDY I have followed the exchanges between Drs. Wakayama, Carpenter, and Karpati 011 the topic of dystrophin and its localization in skeletal muscle. I am surprised that so little serious comment has been made on the suitability of immunocytochemistry applied to ultrathin sections of skeletal muscle as a technique to study the localization of dystrophin. Neither Wakayama nor Carpenter and Karpati referred to the definitive study on the localization of dystrophin by Cullen et al.3 who used a monoclonal antibody to the rod domain of dystrophin and immunogold labelling (used first in this type of work by Watkins et a15) to show that the roddomain was localized beneath the plasma membrane of the muscle fibre. Apart from the clarity o f the images produced by immunogold labeling, an additional advantage of immunogold labeling is that it is possible to quantitate the distribution and localization of the protein. T h e use of other specific monoclonal antibodies to defined regions of dystrophin will make it possible to study the localization of various regions of the protein. Such refinement is not possible with the relatively crude technique of immunocytochemistry. John B. Harris PhD Regional Neurosciences Centre Newcastle General Hospital Newcastle upon Tyne NE4 6BE England 1. Carpenter S, Karpati G, Zubrzycka-Gaarn, et al: Dystrophin is localized to the plasma membrane of human skeletal
MUSCLE & NERVE
April 1992
muscle fibers by electron-microscopic cytochemical study. Mzwcle Nerve 1990;13:376-380. Carpenter S, Karpati G : Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electron-microscopic cytochemical study: A reply (letter). MzLrcle Nerve 1991;14:577. Cullen MJ, Walsh J, Nicholson LV, Harris JB: Ultrastructural localization of dystrophin in human muscle by using gold immunolabelling. Proc Roy Sac Lond (Biol) 1990; 240: 197-2 10. Wakayama Y : Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electronmicroscopic cytochemical study (letter). Muscle Nerve 1991; 14:576-577. Watkins S, Hoffman EP, Slayter HS, Kunkel LM: Immunoelectron microscopic localization of dystrophin in myofibres. Nature (London) 1988;333:863-866.
DYSTROPHIN IS LOCALIZED TO THE PLASMA MEMBRANE OF HUMAN SKELETAL MUSCLE FIBERS BY ELECTRON=MICROSCOPIC CYTOCHEMICAL STUDY=A REPLY Although the aim of my letter' was not to include all the references dealing with dystrophin localization, I regret that I did not cite the important article of Cullen et al.' I agree that localization of dystrophin to the inner side of the skeletal muscle plasma membrane can be demonstrated with greater clarity with the use of immunogold-labeled antibodies at the ultrastructural level. In addition, quantitation data are potentially available. However, the immunoperoxidase technique can also provide an accurate localization of the dystrophin molecule in this setting.
Yoshihiro Wakayama, MD, PhD Division of Neurology Department of Medicine Showa University Fujigaoka Hospital Yokohama, 227 Japan 1. Cullen MJ, Walsh J , Nicholson LVB, Harris JB: Ultrastructural localization of dystrophin in human muscle by using gold irnniunolabelling. Proc Roy Soc Lond (Biol) 1990;240: 197-2 10. 2. Wakayama Y: Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electronmicroscopic cytochemical study. Muscle Newe 1991;14576577.
POLYGLUCOSAN BODY DISEASE In their article, Cafferty et all presented 2 patients who had clinical signs which they claimed were peculiar to polyglucosan body disease. T h e patients were older than 50 and had both peripheral neuropathy and myelopathy with urinary incontinence. T h e authors discussed that polyglucosan body found in the sural nerve biopsies of their patients wasn't specific for the disease which has been reported in only 15 patients. In fact
Letters to the Editor
polyglucosan body can be found in other diseases and in healthy subjects. Dementia was present in 8 of 15 cases of polyglucosan body disease reported in the literature. Symptoms began in the fifth or sixth decade and continued for 3 to 20 years.5 Vitamin B,, deficiency is manifested in the peripheral nervous system by the signs and symptoms of neuropathy and in the central nervous system by myelopathy, optic atro hy, and dementia.3 Optic atrophy is rare. Chanarin estimated an incidence of 0.3% in patients with this disease. Contrary to the opinion of Cafferty et al, the toristellation of peripheral nerve and central disorders with sphincter problems should first suggest subacute combined degeneration of the spinal cord due to vitamin B,, deficiency. T h e disease usually progresses over several weeks or months; however, it may be rapid or may be more chronic, developing over a year or more. Electrophysiological studies indicate the neuropathy to be secondary to a dying-back type of axonal degeneration. Neuropathological studies have demonstrated loss of large myelinated fibers in distal sensory nerves as well as axonal degeneration in individually teased fiber preparation^.^ Hematological findings such as megaloblastic anemia is not a must in subacute combined degeneration of the spinal cord.3 The determination of serum vitamin B,, level is essential in the diagnosis of the treatable condition of vitamin B deficiency. T h e diagnosis of polyglucosan body disease, which has similar neurologic and neurophysiologic properties, could only then be considered.
f '
Musa Onar, MD Department of Neurology Ondokuz Mayis University Medical Faculty 55139 Samsun, Turkey. 1 . Cafferty MS, Lovelace RE, Hays AP, et al: Polyglucosan body disease. Muscle Nerve 1991;14:102- 106. 2 . Chanarin I: Pernicious anemia and other vitamin B,, deficiency states. Abstr World Med 1970;44:73. 3 . Davies-Jones GAB: Neurologic manifestations of hematological disorders, in Aminoff MJ (ed): Neurology and Crnerul Medicine. New York, Churchill Livingstone, 1989, pp 188. 4. Fine EJ, Soria E, Pdroski MW et al: The neurophysiological profile of vitamin B,, deficiency. Muscle Nerve 1990;13: 152- 164. 5. Gray F, Gherardi R, Marshall A, et al: Polyglucosan body disease. ,I Neuroputh Exp Neurol 1988;40:459-474.
POLYGLUCOSAN BODY DISEASE: A REPLY Dr. Musa Onor's comments on the similarity of the manifestation of B 12 deficiency and polyglucosan disease are important. B,, deficiency should be entertained in the differential diagnosis of patients presenting with the constellation of dementia, myelopathy, and neuropathy as described in our article.
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In current times HIV should also be routinely tested on these patients. Maureen S. Cafferty, MD Department of Medicine Neurology Division St. Luke's/Roosevelt Hospital Center 114th Street & Amsterdam Avenue New York, N.Y. 10025 Robert E. Lovelace, MD Arthur B. Hays, MD Serenella Surides, MD Salvatore Di Mauro, MD Lewis P. Rowland, MD Neurological Institute College of Physicians and Surgeons Columbia University New York, N.Y. 10032
CONDUCTION BLOCK IN HEREDITARY MOTORANDSENSORYNEUROPATHY TYPE I Conduction block has been encountered in several acquired neuropathies during the past decade and is a
A Wrist
0.2 ms
characteristic feature of some of these.',' Although the concept of conduction block is receiving increasing attention, several problems attached to its assessment seem to remain underemphasized. First, there is no agreement about its electrophysioSecond, it may be hazardous to logical definition. apply the criteria used to define conduction block in acute demyelinating neuropathies to chronic disorders because in the latter partial denervation is frequently present. A third problem, i.e., attaining supramaximal stimulation, was experienced by us investigating patients with hereditary motor and sensory neuropathy type I (HMSN I). We studied 37 patients, aged 4 to 67 years, from six families with autosonial dorninantly inherited HMSN I . CMAPs were recorded from the abductor pollicis brevis muscle after percutaneous stimulation of the median nerve at the wrist and at the elbow with rectangular pulses of 0.1 ms duration and a maximuni amperage of 80 mA. T h e electrodes, the anode being held proximally along the nerve, were carefully placed at the optimal site. Surface forearm temperature was 3 2 - 34" C. Conduction block was considered to be present if
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20 mA .-_I .
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- 40mA -
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Elbow
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FIGURE 1. Compound muscle action potentials recorded from the abductor pollicis brevis muscle after stimulation of the median nerve at the wrist and at the elbow in two patients (A and B) with HMSN I. Note the differences in calibration.
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the proportional CMAP amplitude decrease on proximal as compared with distal stimulation was at least 50%, provided that the proportional increase in CMAP duration was 15% o r less. Nine individuals (25%) met these criteria, four of them showing CMAP amplitude reductions of more than 80%. However, supramaximal stimulation may not have been attained. Therefore, three individuals were reexamined using longer stimulus durations. In one, conduction block appeared to be absent with supramaximal stimulation of 0.2 ms duration. In another, conduction block may o r may not have been present, since strong stimuli lasting 0.2 ms were too painful to allow supramaximal stimulation (Fig. IA). In the third subject, conduction block was present on supramaximal stimulation lasting 0.3 ms (Fig. lb). Our data show that differentially decreased nerve excitability may quite easily cause an electrodiagnostic artifact mimiciking conduction block and emphasize the necessity of longer-duration, often painful stimuli in HMSN I, and probably also in other disorders. This has implications for the usefulness of conduction block in the distinction between acquired and inherited demyelinating polyneuropathies as proposed by Lewis and Sumner.' This distinction may indeed be difficult at times, especially if no family data are available to confirm heredity. In support of the findings of O h and Chang,3 our observations indicate that caution should be exercised in using conduction block as a diagnostic tool. T h e occurrence of a large CMAP amplitude reduction on proximal stimulation, irrespective of whether this represents true of "false" conduction block, does not preclude the possibility of HMSN 1. These patients should be tested for the presence of the duplication in chromosome 1 7 ~ 1 1 . 2which , we recently demonstrated to be most likely a mutation responsible for HMSN Ia."
Jessica E. Hoogendijk, MD* Marianne de Visser, MD, PhD* Lo J. Bout, PhD* Frans G.I. Jennekens, MD, PhDt Bram W. Ongerboer, MD, PhD* *Department of Neurology Academic Medical Center 1105 AZ Amsterdam The Netherlands tDepartment of Neurology Academic Hospital Utrecht Utrecht The Netherlands 1. Brown WF, Feasby TE: Conduction block and denervation in Guillain- Barre polyneuropathy. Brain 1984;107:219239. 2. Lewis RA, Sumner AJ: T h e electrodiagnostic distinction between chronic familial and acquired demyelinative neuropathies. Neurology 1982;32:592- 596. 3. O h SJ, Chang CW: Conduction block and dispersion in hereditary motor and sensory neuropathy. Muscle Nerve, 1987;10:656A. 4. Pestronk A , Chaudhry V, Feldman EL, Griffin J W , Cornblath DR, Denys EH, et al. Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnor-
Letters to the Editor
malities, and high titers of aritiglycolipide antibodies. Ann Neurol 1900;27:316-326. 5. Raeymaekers P, Timmerman V, E Nelis, De Jonghe P, J E Hoogendijik, F Baas, et al. Duplication in Charcot-MarieToorh neuropathy type la(CMT1a) Neuromusc Disord 1991;1:93-97.
CONDUCTION BLOCK IN HEREDITARY MOTOR SENSORY NEUROPATHY, TYPE I: CASE REPORT Supramaximal stimulation is the most important technical parameter required for an adequate motor nerve conduction study.' Supramaximal stimulation should be achieved by adjustment of the stimulus duration as well as its intensity. Stimulus parameters should not be limited to the certain parameters as Hoogendijk et a1 did in the initial test.' In HMSN type I, for example, a stimulus duration longer than 0.1 ms is needed in a majority of cases, as observed by these authors in the later test. T h e following case report illustrates this technical point and presents the core message in our study." A 32-year-old white man had difficulty running and had had a high arched foot since childhood. The diagnosis of HMSN Type I was made in his grandmother, father, and son. He had had progressive weakness in the legs for the previous 2 years. Examination showed 3-0 MRC strength in the anterior tibialis and gastrocnemius muscles, pes cavus, diffuse atrophy in the lower leg, thick peroneal nerves at the fibular head, and sensory impairment below the mid-shin level. The s u r d nerve biopsy showed prominent "onion-bulb formation." The nerve conduction study showed no response in the peroneal and posterior tibia1 nerves with the maximal stimulation parameters available on the EMG machine (0.5 msi99 mA). In the median and ulnar nerves, the motor nerve conduction velocity showed uniform slowing between the segments as well as between the nerves (Fig. 1). In the median nerve, conduction block (48% to 61% decrease) was observed in the wrist-elbow segment by the peak-to-peak and negative-amplitude, and negative- and total-area methods. In the ulnar nerve, conduction block (45% to 60% decrease) was observed in the above elbow and axilla segment by all four methods. These values were clearly outside the normal 2 S.D.2 In this case, supramaximal stimulation mean was achieved with a stimulus duration of 0.5 ms and stimulus intensity of 65 to 87 mA. These data indicate that a conduction block exists over the wrist-elbow segment in the median and the above elbow-axilla segment in the ulnar nerves by the best available practical method (area method). This case illustrates several points: (1) supramaxima1 stimulation should be achieved by the adjustment of stimulus duration and intensity. T h e limitation should be the maximum available duration and intensity of a given EMG machine; and (2) conduction block exists even in the presence of uniform nerve conduc-
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tion slowing. Conduction block is not necessarily indicative of “focal” demyelination, but could well be an expression of diffuse demyelination over that segment. Differentiation between the two mechanisms should be studied by short-segment stimulation technique. ‘1’0 guarantee adequacy, our study was done prospectively. We found conduction block in 28% of cases when the data from the median and ulnar nerves were analyzed following Lewis’s method.“ Case B in Hoodgendijks sLudy confirms the finding in our abstract.
T h e core message of our abstract is that differentiation between HMSN type 1 and chronic inflammatory demyelinating polyneuropathy (CIDP) is not possible with the nerve conduction study alone in a substantial number of cases.
Shin J. Oh, MD Department of Neurology
The University of Alabama at Birmingham, UAB Station Birmingham, Alabama 35294
Median Nerve Latency PP-amplitude NP-amplitude N-duration T-duration N-area T-alYa
NP-amplitude N-duration T-duration N-area T-area
15.10 3.73 2.01 7.70 19.10 7.65 16.10
NCV
14.20
NCV PP-amplitude
r&
w
630 8.00 5.19 7.30 21.60 14.80 3750
-53.4 % -61.3 % +5.4 % -11.6% ‘ -48.3 % -57.190
Ulnar Nerve Latency
6.20
NCV
14.8
BE
AE Ax
NCV PP-amplitude NP-amplitude N-duration T-duration N-area T-area
20.70 5.74 333 9.50 32.20 12.70 30.70
NCV PP-amplitude NPamplitude N-duration T-duration N-area T-area
15.64 2.96 138 10.50 29.00 6.95 16.50
-48.4 % -59.79% clO.0 % -9.9 % -45.2 % -46.3 %
FIGURE 1. Conduction block in the wrist (W)-elbow (E) segment in median nerve and in the above elbow (AE)-axilla (Ax) segment in the ulnar nerve. Various electrophysiological data are listed to the right of figures. Latency represents the terminal latency by msec; NCV, nerve conduction velocity by rneterisec; PP-amplitude, peak-to-peak amplitude (L2-L4) by mV; NP-amplitude, negative-peak arnplitude (L1-L2) by mV; N-duration, duration of negative wave (L1-L3) by rnsec; T-duration, duration of total wave (LVL5); N-area, area of the negative wave (Ll-L2-L3) by rnV/msec; and T-area, area of the negative and positive waves (L1-L2-L3-L4-L5). Percentages represent the difference between the repreproximal and distal CMAPs in the segment of conduction block in the various parameters. sents an increase and -, a decrease.
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1. Hoogendijk J E , de Visser M, Bour IJ, Jennkens FGI, Origerboer BW: Conduction block in hereditary motor and sensory neuropathy type I. Mu.scle Nervc 1992;15:520-521. 2. Kim ED, Kuruoglou HR, O h SJ: What is the best diagnostic index of conduction block and temporal dispersion? Muscle Ncme 1991; 14:884. 3 . Lewis RA, Sumner A]: T h e electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies. Neurology 1982;32:592-596. 4. Oh SJ: Clinical Electromyography: Nerve Conduction Studies. Baltimore, University Park Press. 1984. 5. Oh SJ, Chang CW: Conduction block and dispersion in hereditary motor and sensory neuropathy. Muscle Nerve 1987;10:656A.
CONDUCTION BLOCK I N HEREDITARY MOTORANDSENSORYNEUROPATHY TYPE I: A REPLY I appreciate the opportunity to respond to letters commenting upon the electrophysiologic criteria for distinguishing between acquired and hereditary chronic demyelinating neuropathies advanced by Dr. Richard Lewis and me some 9 years ago.:! It is gratifying that these criteria have received such general acceptance over the past decade. It is also not surprising that they might require some modification after this length of time. T h e two letters draw attention to the presence of “conduction block” in some cases of HMSN 1. I d o not accept that these are examples of bonefide conduction block. It is now widely recognized that a drop in ampli-
Letters to the Editor
tude and area of the distal to proximal CMAP responses is occasionally encountered in motor conduction studies of nerves associated with advanced chronic denervation from whatever cause, because of the problems created by positive- negative interphase cancellation of the few remaining large polyphasic motorunit potentials. Under these conditions conduction block can only be established if it is clearly restricted to localized nerve segments, or if by identifying all individual recruitable motorunits it can proven that their summed responses cannot reconstitute the distally evoked CMAP. I would also like to remind readers that the presence or absence of conduction block is not the most important of the criteria to use in clinical practice in distinguishing the chronic hereditary from chronic idiopathic demyelinating polyneuropathy (CIDP). It is the remarkable uniformity of the conduction slowing along all segments of all peripheral myelinated axons that so characterizes the electrophysiologic abnormality of HMSN 1 . By contrast CIDP usually shows multifocal or segmental conduction changes. Austin J. Sumner, MD Department of Neurology LSU Medical Center 1542 Tulane Avenue New Orleans, Louisiana 70112
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1. Cornblath DR, Sumner AJ, Daube J et al: Conduction block in clinical practice. Muscle Nerve 1991;14:809-871. 2. Lewis RA, Sumner AJ: T h e electrodiagnostic distinction between chronic familial and acquired demyelinative neuropathies. Neuroloa 1982;32:592-597.
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