NEUROPATHY IN MYOTUBULAR OR CENTRONUCLEAR
MYOPATHY
ROBERTO E. P . SICA * OLGA P . SANZ * *
In 1966 Spiro, Shy and Gonatas
1 2described a congenital myopathy in a
12yearold boy whose muscle biopsies revealed small myofibers with centrally
located nuclei that were surrended by a clear area. Histochemically the cen
tral region of the myofibers showed disturbed enzymatic activity and ultrastruc
turally the nuclei were associated with myelin figures, glycogen granules and
mitochondriae. The authors called this condition "myotubular myopathy" be
cause the muscle fibers resembled the myotubes seen in early fetal life.
Since then several reports have appeared in the literature generally re
garding the syndrome as myopathic (Ortiz de Zarate and Maruffo
7, 1970; Sher,
Rimalovski, Athanassiades and Aronson
9, 1967; Kinoshita and Cadman
4, 1968;
Bethlen, van Wijngaarden, Mumenthaler and Meijer
1, 1970; Schochet, Zellwe
ger, Ionasescu and McCormick
81972; Campbell, Rebeiz and Walton
21969),
though neuropathic features, namely distal atrophy (Ortiz de Zarate et al.
71970; Spiro et a l .
1 21966; Sher et al.
91967; Schochet et al.
81972), hypo or
arreflexia (Ortiz de Zarate et al.
71970; Spiro et a l .
1 21966; Kinoshita et al.
41968, Schochet et al.
81972; Engel, Gold and Karpati
3, 1968), electromyogra
phic fibrillation potentials (Spiro et a l .
1 21966; Bethlem et a l .
11970, Engel et
al.
31968) and histological muscle fibers grouping (Spiro et. a l .
1 21966, Engel
et a l .
31968) have been also described in this entity.
These studies clearly indicate the need for a quantitative investigation of
motor unit function in this "myopathy". Recently we have described some
electrophysiological methods which enables estimates to be made of the num
ber and sizes of motor units in the small muscles of the foot (McComas, Faw
cett, Campbell and Sica
5, 1971) and hand (Sica, McComas, Upton and Long
mire
1 1, 1974) and in the soleous muscle (Sica, Sanz and McComas, umpu
blished results).
The application of these techniques to the study of this condition provided
• electrophysiologica
l evidences that neuropathic changes do occur.
* Sección de Electroneurofisiologia Clínica, Servicio de N e u r o l o g í a , Hospital R a m o s Mejía, Buenos Aires; ** Municipalidad de la Ciudad de Buenos Aires Medical R e search Council Scholar.
Acknowledgement — T h e authors are indebted to Dr. Ortiz de Z á r a t e for per
M A T E R I A L
T h e patient submitted to investigation w a s a 34yearold white m a n who clini c a l l y and histologically proved to suffer from centronuclear or m y o t u b u l a r m y o p a t h y a s he w a s published by Ortiz de Z a r a t e and M a r u f f o 7
elsewhere w i t h such diagnosis (Case 1, A . K . ) .
M E T H O D S
T h e methods employed for studying the n u m b e r and sizes of m o t o r units and impulse conduction in m o t o r nerve fibers h a v e been described elsewhere ( M c C o m a s et a l . 5
, Sica et al. " ) as w e l l as the technique employed for repetitive s t i m u l a t i o n of the m o t o r nerve fibres (Sica and M c C o m a s1 0
) .
F o r sensory conduction velocity recordings were m a d e with two chlorided silver discs e a c h one cm in d i a m e t e r spaced three c m appart in a plastic holder. E x c e p t for the sural nerve, all recordings were m a d e of orthodromically conducted impulses. T h e limbs w e r e w a r m e d w i t h an infrared l a m p prior to study and the a m b i e n t t e m perature w a s m a n t a i n e d a t a b o u t 25°C.
F o r t h e studies of the of the extensor d i g i t o r u m brevis m u s c l e a t o t a l of 4 5 h e a l thy subjects below t h e a g e of 6 0 served as controls. F o r the t h e n a r m u s c l e s 67 con trol m u s c l e s w e r e employed, for hypothenar 80 and for soleus 7 5 .
For the sensory studies 5 5 subjects acted as controls.
R E S U L T S
Motor and sensory nerve conduction velocities as well as amplitudes of sensory action potentials were well within n o r m a l limits in the upper and lower limbs ( T a ble 1 ) .
A decremental response in the thenar m u s c l e s evoked potential to repetitive m e dian n e r v e stimulation a t the wrist w a s observed in this patient. T h e r e were no> differences between the a m p l i t u d e s of the first and last evoked potential w h e n tested with one second train of s u p r a m a x i m a l stimuli a t frequencies of 3 or 1 0 H z ; h o w e v e r a t 50 H z 8 0 % decrease w a s evident.
Conventional electromyographic studies were done in p r o x i m a l and distal m u s cles of the upper and lower limbs. A m i x e d to interference pattern w a s recorded in all them, the individual potentials w e r e m a i n l y of reduced duration and a m p l i t u d e in p r o x i m a l muscles, whilst in t h e distal groups they were m a i n l y poliphasic and of incresead amplitude.
N e i t h e r fibrillations nor positive sharp w a v e s were observed. N o myotonic dis charges w e r e recorded.
D I S C U S S I O N
The above observations suggest that the disease is neurogenically deter
mined and support Engel et al.
3(1968) earlier postulation who made the as
suption that the pathological process might be due to "functional deficiency of
maturational factor from the motor nerves".
In terms of the "sick" motoneurone hypothesis (McComas, Sica and Camp
bell
6, 1971) the entity might be interpreted as due to an inability of the skeleto
motor neurone to drive or to maintain the muscle fiber in a complete mature
state, establishing a defective relationship between its axon and the muscle fi
bers which would account for a later functional denervation.
As most of the cases reported in the literature show a progressive
downhill course, it is sensible to assume that the whole motoneuronal population
is "sick", this situation could explain the lack of increased size of the remainer
functional units for they would be unable to branch their axons or grow new
axonal sprouts; it can also explain the decremental muscle response to high
repetitive stimulation as impaired neuromuscular transmission is other feature
which characterizes the "sick" motoneurone.
If Engel et al.
3assumption that the defect in the relationship between
the muscle fibers and their innervation should be produced early in the de
velopment of the muscle, before the 20th fetal week, it can be postulated that
by then most of the motoneurones should be already ill.
S U M M A R Y
R E S U M E N
Un estudio electrofisiológico detallado fué hecho en los músculos extensor
corto de los dedos, de la eminencia tenar, de la eminencia hipotenar y soleo
en un paciente con el diagnóstico de miopatía miotubular o centronuclear. El
hallazgo principal fué una notoria reducción en el número de unidades motoras
activas en todos los músculos investigados, en tanto que las unidades
rema-nentes mostraron tamaño conservado. Las observaciones hechas se han
in-terpretado como favoreciendo la génesis neurógena en el desarrollo de este
proceso.
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