Continuous Muscle Fibre Activity: a Case Treated with Acetazolamide

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J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.64.2.256 on 1 February 1998. Downloaded from 256 J Neurol Neurosurg Psychiatry 1998;64:256–258

SHORT REPORT

Continuous muscle ﬁbre activity: a case treated with acetazolamide

Nes¸e Çelebı˙soy, Zafer Çolakogˇlu, Yaprak Akbaba, Nur Yüceyar

Abstract daily, was admitted to hospital because of an A case is reported of the continuous mus- increase in cramps and muscle stiVness. On cle fibre activity syndrome, which in- examination, the muscles were stiV with gener- cludes a group of disorders characterised alised myokymia, more prominent in distal by sustained motor unit activity due to lower limbs. Calf muscles were hypertrophic hyperactivity of peripheral nerve motor with bilateral pes cavus and hammer toe axons. In this patient the muscle stiVness deformities. The reflexes were lost bilaterally in and myokymic movements were success- the lower limbs. The remainder of the examin- fully treated with acetazolamide, which ation was normal. Her medical history was acts as a membrane stabiliser either by insignificant. Needle EMG showed continuous blockade of chloride and bicarbonate motor unit activity with myokymic discharges. membrane transport or by producing After repetitive stimulation of the motor kaliuresis and raising the transmembrane nerves, after-discharges were recorded. Nerve potential by decreasing extracellular po- conduction studies showed segmental demyeli- tassium. nation, more prominent in motor nerves. The (J Neurol Neurosurg Psychiatry 1998;64:256–258) function of the motor end plates was normal. Keywords: continuous muscle fibre activity syndrome; Complete blood count, sedimentation rate, acetazolamide routine blood biochemical analysis, protein and immune electrophoresis, antinuclear anti- body, anti-DNA, and rheumatoid factor were Continuous muscle fibre activity and the in the normal range. No abnormality could be eponym Isaacs’ syndrome describes a heteroge- detected in abdominal and pelvic ultrasonogra- neous group of conditions that exhibit sus- phy and in thorax CT. On admission, car- tained, diVuse motor unit activity due to bamazepine was stopped and 25 mg lamot- hyperactivity of peripheral nerve motor rigine; also a sodium channel blocker, was http://jnnp.bmj.com/ axons.1–3 These conditions can either be associ- given daily. After a week, the patient refused to ated with clinical or EMG evidence of periph- use the drug as cramps, generalised twitching, eral neuropathy or not and generally respond to and muscle stiVness became very disturbing. either phenytoin or carbamazepine, which are The next drug tried was mexiletine. She was voltage dependent sodium channel blockers.4 given 200 mg twice daily for one week. The patient reported it to be better than lamotrigine Case report but not as good as carbamazepine. Acetazo-

A 38 year old woman, who was diagnosed as lamide was the third choice and a dramatic on September 23, 2021 by guest. Protected copyright. having Isaacs’ syndrome 12 years ago and relief was reported by the patient after doses of treated with 200 mg carbamazepine three times 250 mg twice daily. The muscle stiVness Ege University, Faculty of Medicine, Department of Neurology, Bornova, ~Izmir, 35100, Turkey N Çelebı˙soy Z Çolakogˇlu Y Akbaba N Yüceyar

Correspondence to: Dr Nes¸e Çelebisoy, Ege University Faculty of Medicine, Department of Neurology, Bornova,~ Izmir, 35100, Turkey. Telephone 00232 3880980; fax 00232 3422141.

Received 14 May 1997 and in revised form 21 July 1997 Figure 1 (A) Bursts of repetitively ﬁring motor unit potentials recorded from the soleus muscle during treatment with Accepted 29 July 1997 carbamazepine. (B) Supression of the activity during treatment with acetazolamide. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.64.2.256 on 1 February 1998. Downloaded from Continuous muscle ﬁbre activity 257

Figure 2 (A) After-discharges recorded from the soleus muscle by stimulation of the tibial nerve at the knee during treatment with carbamazepine. (B) Disappearance of the after-discharges during treatment with acetazolamide.

regressed and myokymic movements became cle transmembrane potential.10 Familial ataxia nearly invisible. In the needle EMG, the and myokymia is another hereditary disorder in continuous motor unit activity was supressed which acetazolamide is used. Brunt et al12 (fig 1) and the after-discharges recorded after found acetazolamide to be eVective in sup- motor nerve stimulation had disappeared pressing the ataxic episodes, although there was (fig 2). The patient used the drug for three an increase in continuous motor unit activity. weeks with appreciable recovery, but found In a patient described by Vaamande et al13 acral paraesthesia too disturbing to continue acetazolamide was of no therapeutic value in and asked to change back to carbamazepine. suppressing the ataxic episodes. Molecular She is now back on carbamazepine therapy. genetic advantages have led to identification of Acetazolamide is an unsubstituted sulphona- two distinct autosomal dominant disorders mide. Its main biochemical action is the inhibi- characterised by episodic ataxia; episodic tion of carbonic anhydrase, an enzyme distrib- ataxia type I is caused by mutations in the uted widely in the brain and other tissues. potassium channel gene (KCNA 1) on chro- Besides being a diuretic agent, it is used in mosome 12.14 The cause of episodic ataxia type diverse neurological disorders. Carbonic anhy- II is not yet identified. The eVect of acetazola- drase is found in glial cells and myelin. Its inhi- mide in the prevention of ataxic episodes is bition in the brain causes a rise in total brain related to its negative eVect on neuronal excit- carbon dioxide concentrations and also a ability which is non-specific.12 The mechanism blockade of chloride and bicarbonate mem- leading to hyperactivity of the peripheral nerves brane transport and increases the transmem- in continuous muscle fibre activity is not clear. brane chloride gradient. This is its mechanism Sinha 15 and Newsom-Davis and Mills16 of action in epilepsy.5 It is used in the prophy- et al postulated that the increased nerve terminal http://jnnp.bmj.com/ lactic treatment of hypokalamic periodic pa- excitability could be due to interference with ralysis. The mechanism of action is uncertain. function of slowly activating potassium chan- Because acidosis retards the influx of potassium into cells, the metabolic acidosis pro- nels that normally stabilise the membrane duced by acetazolamide has been postulated to potential. Antibodies to voltage gated potassium channels have been detected in some be the mechanism of action in hypokalaemic 17 periodic paralysis.6–8 On the other hand, aceta- patients. Phenytoin and carbamazepine is zolamide may produce a non-acidosis depend- eVective in most, but not all, patients. This on September 23, 2021 by guest. Protected copyright. ent alteration of muscle membrane function eVect is due to reduced flux of sodium ions during action potentials.4 Mexiletine; a sodium that results in a decreased net flux of potassium 18 into muscle. This alteration of muscle mem- channel blocker, also proved to be eVective. brane function may relate in part to acetazola- Acetazolamide was first used by Mertens and 19 mide’s beneficial eVect in hypokalaemic peri- Zschoke in cases of neuromyotonia and a odic paralysis.9 Acetozolamide responsive reduction in resting muscle activity was de- myotonia congenita, first described by Trudell tected. On the other hand, Brunt et al12 found et al10 resembles Thomsen’s disease in appear- that there was an increase in continuous ance except for painful muscle stiVness.11 Myo- muscle fibre activity in patients with familial tonia is provoked by fasting and oral potassium ataxia and myokymia when acetazolamide was and relieved by carbohydrate, similar to hyper- given. In our patient a dramatic relief was kalaemic paralysis, although paralysis is not a found with acetazolamide. The mechanism of feature. Acetazolamide tends to provide dra- action is membrane stabilisation, which can matic relief. An increase in the ratio of either be achieved by blockade of chloride and extracellular to intracellular potassium would bicarbonate membrane transport as it is be expected to decrease the muscle fibre trans- proposed in epilepsy or by producing kaliuresis membrane potential and render it more liable and raising the transmembrane potential by to depolarisation. Acetazolamide administra- decreasing extracellular potassium as it is pro- tion produces a kaliuresis and decrease in posed in acetazolamide responsive myotonia. extracellular potassium and may raise the mus- Whatever the mechanism is, acetazolamide can J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.64.2.256 on 1 February 1998. Downloaded from 258 Çelebı˙soy, Çolakogˇlu, Akbaba, Yüceyar

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