LETTERS TO THE EDlTOR
A NEW INSTRUMENT FOR OBTAINING TISSUE BIOPSY OF MUSCLE Biopsy of muscle for histopathological evaluation requires that the tissue be clamped at the time of excision to prevent contraction which causes microscopic artifacts. Biopsy instruments currently available use a variety of clamping techniques to provide muscle from which the pathologist can cut well-oriented longitudinal and cross-sections, but none of these clamps is entirely satisfactory for reasons of design or fabrication. What is needed is a c h i p which is simple and certain in its application, which requires only one hand for its use, which can be used for dissection, and which will grip the biopsy tissue firmly enough to prevent shortening. The instrument should be sized to fit into a standard specimen jar. T h e instrument here described (Fig. 1) incorporates: 1 . A two-pronged, tooth-serrated, slender, tapered I 0 mm fork-jawed tip, which assures easy access to muscle and can be used to spread and dissect out a proper portion of tissue, retaining a histologically adequate, well-oriented biopsy specimen, providing hemostasis within the specimen, and preventing contraction after it has been clamped and dissected free.
’
FIGURE 1. Stat-Grip muscle biopsy clamp, manufactured and distributed by Tri-State Hospital Supply Corporation, 301 Catrell Drive, P.O.B. 170, Howell, Michigan 48843.
2. Ring handles and ratchet-action locking, providing improved pressure control that can be regulated by one hand, guaranteeing a secure grip on the biopsy specimen. 3. A 30-degree angulation of the grasping end of the clamp, which warrants optimal operative site visualization during dissection and affords easier access to deeper tissues. 4. Design and construction features that are balanced and weighted for comfort and function. This instrument has to date been successfully used with facility and satisfaction in 60 muscle biopsies (particularly where deep dissection was required). Irwin M. Siegel, MD Department of Neurological Sciences Rush- Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60640 1. Carpenter S, Karpdti G: Patholoa of Skrletal Mwrlr. New York, Churchill Livingstone, 1984.
HEREDITARY MOTOR AND SENSORY NEUROPATHY In a recently published review article on hereditary motor and sensory neuropathy (HMSN) type I, Dr. Chad emphasized the differential points between HMSN type 1 and acquired demyelinating neuropathy.‘ Quoting previous work^,^.^ he stated that “acquired demyelinating neuropathy demonstrates electrophysiologic features not seen in HMSN type I, such as conduction block, dispersed compound muscle action potentials, and differential slowing of conduction velocity.” It is interesting that this rule was broken in the daughter. Data in Table 2 showed “conduction block” between the wrist and below-elbow segment (1.2 mV/ 2.8 mV; 57% decrease in amplitude). There was also a 36% increase in duration in the ulnar nerve study, which is typical of dispersion phenomenon. Clearly, these findings indicate that there was a focal demyelination in the ulnar nerve. Even in the father’s data (Table l ) , there was a 3 1 %
MUSCLE & NERVE
January 1991
85
decrease in the CMAP amplitude in the ulnar nerve. Though this may be “normal” for some, it represents “conduction block” for others.’ It is also intriguing to see a subtle but definite change in the shape of the CMAP with ulnar nerve stimulation at the elbow. Unfortunately, A in Figure 2 does not show the entire montage of the CMAP, which should include the positive deflection. These points raise an interesting question: Can we really differentiate acquired demyelinating neuropathy from HMSN type I on the basis of motor conduction data alone? Our study5 showed that this is not possible in 28% of cases. Shin J. Oh, MD Department of Neurology University of Alabama at Birmingham Birmingham, AL 35294 1. Bernstead TJ, Kuntz NL, Miller RG: Electrophysiologic profile of Dejerine-Sottas disease (HMSN 111) (abstract) Mwcle Nerve 1985;8:625-A. 2. Chad DA: AAEE Case Report # 20: Hereditary motor and sensory neuropathy, type I. Mwcle Nerve 1989;12:875-882. 3. Lewis RA, Sumner AJ: T h e electrodiagnostic distinctions between chronic familial and acquired demyelinating neuropathies. Neurology 1982;32:592-596. 4. Miller RG, Gutmann L, Lewis RA, Sumner AJ: Acquired versus familial demyelinative neuropathies in children. Mwcle Nerve 1985;8:205-210. 5. O h SJ, Chang CW: Conduction block and dispersion in hereditary motor sensory neuropathy. Mwcle Nerve 1987; 10:656-A.
HEREDITARY MOTOR AND SENSORY NEUROPATHY: A REPLY The nerve conduction studies of the patients with HMSN I that were described in the AAEE Case Report‘ disclosed prolonged distal motor and sensory latencies and marked slowing of motor nerve conduction velocity. In most nerves tested, there was only minimal drop-off in amplitude between distal and proximal stimulating sites, and temporal dispersion was mild, within the range of values seen in patients with HMSN I.‘ As noted by Dr. Oh, in two nerves (the ulnar nerve of the father, and the ulnar nerve of the daughter) there were greater degrees of amplitude drop-off and temporal dispersion than is customarily seen in HMSN I , but the overall pattern formed by the abnormalities was indicative of an evenly distributed demyelinating disorder affecting all nerve segments of almost all motor nerves. Dr. Oh’s observations3 are interesting and worthy of further study, but at least in the subjects (father and daughter) of this case report the neurodiagnostic features alone were strongly indicative of HMSN I. David A. Chad, MD Department of Neurology University of Massachusetts Medical Center Worcester, MA 01655
86
1. Chad DA: AAEE Case Report #20: Hereditary motor and sensory neuropathy type I: Muscle Nerve 1989; 12:875-882. 2. Lewis RA, Sumner AJ: T h e electrodiagnostic distinctions 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.
ELECTROPHYSIOLOGY OF ACETYLCHOLINESTERASE INHIBITION IN MYASTHENIA GRAVE Acetylcholinesterase (AChE) inhibition due to organophosphate intoxication is associated with (1) compound muscle action potentials (CMAP) with repetitive discharges and ( 2 ) repetitive nerve stimulation induced decrement-increment and decrement phenomena with mild and severe stages of intoxication respectively.’ The decrement- increment phenomenon has previously been described only with organophosphate poisoning.’ We recently encountered the phenomenon in a 18-year-old patient with documented myasthenia gravis being treated with increasing doses of pyridostigmine for diplopia. Median nerve stimulation evoked CMAPs with repetitive discharges at dosages of pyridostigmine between 180 and 420 mg, and these became more prominent following 10 mg intravenous edrophonium. At 2 Hz and 5 Hz nerve stimulation, repetitive discharges occurred with all CMAPs in a train. They were seen only following the initial CMAP at 20 Hz stimulation. At pyridostigmine doses of 240 mg and greater, the decrement-increment response occurred at 10 Hz and 20 Hz nerve stimulation 1-4 minutes following 10 mg intravenous edrophonium (Figure 1). No weakness or cholinergic symptoms occurred at this time. Repetitive discharges following a single CMAP in the presence of AChE inhibition reflect excess available acetylcholine and result from both antidromic backfiring in the terminal axons5 and prolongation of postsynaptic end plate potential^.^ They are the earliest electrophysiological abnormality in organophosphate poisoning as was the case in our patient.’ Repetitive nerve stimulation at increasing frequencies abolishes backfiring and the repetitive discharges following the CMAP. This occurred in our patient at rapid rates of stimulation. In the decrement-increment response, the decrement is maximal with the second CMAP in the series followed by recovery of CMAP amplitude. T h e subsequent CMAP amplitudes never exceed that of the initial CMAP except for pseudofacilitation at higher rates of repetitive nerve stimulation. T h e phenomenon reflects light stages of AChE inhibition during which antidromic backfiring is prominently seen with the first CMAP of the series at rapid rates of stimulation and not with subsequent CMAPS.’ T h e lack of antidromic axonal backfiring with the second and subsequent nerve stimuli
’.*
MUSCLE & NERVE
January 1991
the time of mild AChE inhibition prior to weakness or during the recovery period. T h e decrement-increment response is distinctly different from the decrement phenomenon characteristic of the basic physiological defect in myasthenia gravis and must be differentiated from it. Its presence is not associated with weakness but predicts potential cholinergic crisis, although the latter is now rarely seen with myasthenia gravis.
’
’i~wvvvvvvvvv before edrophonium 10 mg I V
.
1.5 minutes later
J5 r n ~ 5ms FIGURE 1. Trains of CMAPs recorded at 20 Hz stimulation of median nerve 1.5 hours after pyridostigmine 240 mg. Before edrophonium 10 mg IV was given, pseudofacilitation occurs; 1.5 minutes after edrophonium, the decrement-increment phenomenon occurs with the second CMAP showing the maximum decrement followed by recovery with subsequent stimuli. A repetitive discharge occurs only after the initial CMAP.
likely plays a central role in the CMAP amplitude recovery but the mechanism is not well understood.” T h e occurrence of the decrement-increment phenomenon in our patient after additional AChE inhibition with edrophonium 10 mg intravenously is identical to that described in organophosphate intoxication at
Ludwig Gutmann, MD Department of Neurology West Virginia University School of Medicine Morgantown, WV 26506 Roland Besser, MD Department of Neurology University of Mainz 6500 Mainz, Germany 1 . Besser R, Gutmann L, Dillmann U, Weilemann LS, Hopf HC: End-plate dysfunction in acute organophosphate intoxication. Neurology 1989;39:561-567. 2. Blaber LC, Bowman WC: Studies on the repetitive discharges evoked in motor nerve and skeletal muscle after injection of anticholinesterase drugs. Br J Pharmacol 1963; 20:326-344. Bowman WC, Gibb AJ, Harvey AL, Marshall IG: Prejunctional actions of cholinoceptor agonists and antagonists, and of anticholinesterase drugs. In: Kharkevich DA, ed. New Neuromuscular Blockzng Agents. Berlin: Springer-Verlag, 1986;141- 169. Eccles JC, Katz B, Kuffler SW: Effect of eserine on neuromuscular transmission. J Neurophyszol 1942;5:21 1 - 230. Masland RL, Wigton RS: Nerve activity accompanying fasciculation produced by postigmin. J Neurophysiol 1940; 31269-275.
MUSCLE & NERVE
January 1991
87
A NEW INSTRUMENT FOR OBTAINING TISSUE BIOPSY OF MUSCLE Biopsy of muscle for histopathological evaluation requires that the tissue be clamped at the time of excision to prevent contraction which causes microscopic artifacts. Biopsy instruments currently available use a variety of clamping techniques to provide muscle from which the pathologist can cut well-oriented longitudinal and cross-sections, but none of these clamps is entirely satisfactory for reasons of design or fabrication. What is needed is a c h i p which is simple and certain in its application, which requires only one hand for its use, which can be used for dissection, and which will grip the biopsy tissue firmly enough to prevent shortening. The instrument should be sized to fit into a standard specimen jar. T h e instrument here described (Fig. 1) incorporates: 1 . A two-pronged, tooth-serrated, slender, tapered I 0 mm fork-jawed tip, which assures easy access to muscle and can be used to spread and dissect out a proper portion of tissue, retaining a histologically adequate, well-oriented biopsy specimen, providing hemostasis within the specimen, and preventing contraction after it has been clamped and dissected free.
’
FIGURE 1. Stat-Grip muscle biopsy clamp, manufactured and distributed by Tri-State Hospital Supply Corporation, 301 Catrell Drive, P.O.B. 170, Howell, Michigan 48843.
2. Ring handles and ratchet-action locking, providing improved pressure control that can be regulated by one hand, guaranteeing a secure grip on the biopsy specimen. 3. A 30-degree angulation of the grasping end of the clamp, which warrants optimal operative site visualization during dissection and affords easier access to deeper tissues. 4. Design and construction features that are balanced and weighted for comfort and function. This instrument has to date been successfully used with facility and satisfaction in 60 muscle biopsies (particularly where deep dissection was required). Irwin M. Siegel, MD Department of Neurological Sciences Rush- Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60640 1. Carpenter S, Karpdti G: Patholoa of Skrletal Mwrlr. New York, Churchill Livingstone, 1984.
HEREDITARY MOTOR AND SENSORY NEUROPATHY In a recently published review article on hereditary motor and sensory neuropathy (HMSN) type I, Dr. Chad emphasized the differential points between HMSN type 1 and acquired demyelinating neuropathy.‘ Quoting previous work^,^.^ he stated that “acquired demyelinating neuropathy demonstrates electrophysiologic features not seen in HMSN type I, such as conduction block, dispersed compound muscle action potentials, and differential slowing of conduction velocity.” It is interesting that this rule was broken in the daughter. Data in Table 2 showed “conduction block” between the wrist and below-elbow segment (1.2 mV/ 2.8 mV; 57% decrease in amplitude). There was also a 36% increase in duration in the ulnar nerve study, which is typical of dispersion phenomenon. Clearly, these findings indicate that there was a focal demyelination in the ulnar nerve. Even in the father’s data (Table l ) , there was a 3 1 %
MUSCLE & NERVE
January 1991
85
decrease in the CMAP amplitude in the ulnar nerve. Though this may be “normal” for some, it represents “conduction block” for others.’ It is also intriguing to see a subtle but definite change in the shape of the CMAP with ulnar nerve stimulation at the elbow. Unfortunately, A in Figure 2 does not show the entire montage of the CMAP, which should include the positive deflection. These points raise an interesting question: Can we really differentiate acquired demyelinating neuropathy from HMSN type I on the basis of motor conduction data alone? Our study5 showed that this is not possible in 28% of cases. Shin J. Oh, MD Department of Neurology University of Alabama at Birmingham Birmingham, AL 35294 1. Bernstead TJ, Kuntz NL, Miller RG: Electrophysiologic profile of Dejerine-Sottas disease (HMSN 111) (abstract) Mwcle Nerve 1985;8:625-A. 2. Chad DA: AAEE Case Report # 20: Hereditary motor and sensory neuropathy, type I. Mwcle Nerve 1989;12:875-882. 3. Lewis RA, Sumner AJ: T h e electrodiagnostic distinctions between chronic familial and acquired demyelinating neuropathies. Neurology 1982;32:592-596. 4. Miller RG, Gutmann L, Lewis RA, Sumner AJ: Acquired versus familial demyelinative neuropathies in children. Mwcle Nerve 1985;8:205-210. 5. O h SJ, Chang CW: Conduction block and dispersion in hereditary motor sensory neuropathy. Mwcle Nerve 1987; 10:656-A.
HEREDITARY MOTOR AND SENSORY NEUROPATHY: A REPLY The nerve conduction studies of the patients with HMSN I that were described in the AAEE Case Report‘ disclosed prolonged distal motor and sensory latencies and marked slowing of motor nerve conduction velocity. In most nerves tested, there was only minimal drop-off in amplitude between distal and proximal stimulating sites, and temporal dispersion was mild, within the range of values seen in patients with HMSN I.‘ As noted by Dr. Oh, in two nerves (the ulnar nerve of the father, and the ulnar nerve of the daughter) there were greater degrees of amplitude drop-off and temporal dispersion than is customarily seen in HMSN I , but the overall pattern formed by the abnormalities was indicative of an evenly distributed demyelinating disorder affecting all nerve segments of almost all motor nerves. Dr. Oh’s observations3 are interesting and worthy of further study, but at least in the subjects (father and daughter) of this case report the neurodiagnostic features alone were strongly indicative of HMSN I. David A. Chad, MD Department of Neurology University of Massachusetts Medical Center Worcester, MA 01655
86
1. Chad DA: AAEE Case Report #20: Hereditary motor and sensory neuropathy type I: Muscle Nerve 1989; 12:875-882. 2. Lewis RA, Sumner AJ: T h e electrodiagnostic distinctions 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.
ELECTROPHYSIOLOGY OF ACETYLCHOLINESTERASE INHIBITION IN MYASTHENIA GRAVE Acetylcholinesterase (AChE) inhibition due to organophosphate intoxication is associated with (1) compound muscle action potentials (CMAP) with repetitive discharges and ( 2 ) repetitive nerve stimulation induced decrement-increment and decrement phenomena with mild and severe stages of intoxication respectively.’ The decrement- increment phenomenon has previously been described only with organophosphate poisoning.’ We recently encountered the phenomenon in a 18-year-old patient with documented myasthenia gravis being treated with increasing doses of pyridostigmine for diplopia. Median nerve stimulation evoked CMAPs with repetitive discharges at dosages of pyridostigmine between 180 and 420 mg, and these became more prominent following 10 mg intravenous edrophonium. At 2 Hz and 5 Hz nerve stimulation, repetitive discharges occurred with all CMAPs in a train. They were seen only following the initial CMAP at 20 Hz stimulation. At pyridostigmine doses of 240 mg and greater, the decrement-increment response occurred at 10 Hz and 20 Hz nerve stimulation 1-4 minutes following 10 mg intravenous edrophonium (Figure 1). No weakness or cholinergic symptoms occurred at this time. Repetitive discharges following a single CMAP in the presence of AChE inhibition reflect excess available acetylcholine and result from both antidromic backfiring in the terminal axons5 and prolongation of postsynaptic end plate potential^.^ They are the earliest electrophysiological abnormality in organophosphate poisoning as was the case in our patient.’ Repetitive nerve stimulation at increasing frequencies abolishes backfiring and the repetitive discharges following the CMAP. This occurred in our patient at rapid rates of stimulation. In the decrement-increment response, the decrement is maximal with the second CMAP in the series followed by recovery of CMAP amplitude. T h e subsequent CMAP amplitudes never exceed that of the initial CMAP except for pseudofacilitation at higher rates of repetitive nerve stimulation. T h e phenomenon reflects light stages of AChE inhibition during which antidromic backfiring is prominently seen with the first CMAP of the series at rapid rates of stimulation and not with subsequent CMAPS.’ T h e lack of antidromic axonal backfiring with the second and subsequent nerve stimuli
’.*
MUSCLE & NERVE
January 1991
the time of mild AChE inhibition prior to weakness or during the recovery period. T h e decrement-increment response is distinctly different from the decrement phenomenon characteristic of the basic physiological defect in myasthenia gravis and must be differentiated from it. Its presence is not associated with weakness but predicts potential cholinergic crisis, although the latter is now rarely seen with myasthenia gravis.
’
’i~wvvvvvvvvv before edrophonium 10 mg I V
.
1.5 minutes later
J5 r n ~ 5ms FIGURE 1. Trains of CMAPs recorded at 20 Hz stimulation of median nerve 1.5 hours after pyridostigmine 240 mg. Before edrophonium 10 mg IV was given, pseudofacilitation occurs; 1.5 minutes after edrophonium, the decrement-increment phenomenon occurs with the second CMAP showing the maximum decrement followed by recovery with subsequent stimuli. A repetitive discharge occurs only after the initial CMAP.
likely plays a central role in the CMAP amplitude recovery but the mechanism is not well understood.” T h e occurrence of the decrement-increment phenomenon in our patient after additional AChE inhibition with edrophonium 10 mg intravenously is identical to that described in organophosphate intoxication at
Ludwig Gutmann, MD Department of Neurology West Virginia University School of Medicine Morgantown, WV 26506 Roland Besser, MD Department of Neurology University of Mainz 6500 Mainz, Germany 1 . Besser R, Gutmann L, Dillmann U, Weilemann LS, Hopf HC: End-plate dysfunction in acute organophosphate intoxication. Neurology 1989;39:561-567. 2. Blaber LC, Bowman WC: Studies on the repetitive discharges evoked in motor nerve and skeletal muscle after injection of anticholinesterase drugs. Br J Pharmacol 1963; 20:326-344. Bowman WC, Gibb AJ, Harvey AL, Marshall IG: Prejunctional actions of cholinoceptor agonists and antagonists, and of anticholinesterase drugs. In: Kharkevich DA, ed. New Neuromuscular Blockzng Agents. Berlin: Springer-Verlag, 1986;141- 169. Eccles JC, Katz B, Kuffler SW: Effect of eserine on neuromuscular transmission. J Neurophyszol 1942;5:21 1 - 230. Masland RL, Wigton RS: Nerve activity accompanying fasciculation produced by postigmin. J Neurophysiol 1940; 31269-275.
MUSCLE & NERVE
January 1991
87
![[Clinical practice of hereditary motor neuropathy (HMN) and hereditary sensory and autonomic neuropathy (HSAN)].](/assets/img/hold.png)
