Myokymia

Isaacs syndrome: The disease presents early in life with most patients being < 40 years of age at the time of symptom onset. A dominant mode of inheritance in the familial form of the disease may occur. Progressive painless stiffness, cramping, and weakness are prominent features of the disease. As opposed to fasciculations, patients complain of constant myokymia (writhing movements of the muscles under the skin visualized by continuous "rippling" movements of the muscle). These persist during sleep. Hyporeflexia is also seen in a large percentage of patients. Weakness, when present, tends to be in the distal lower extremities. Autonomic involvement may also be seen with hyperhidrosis and tachycardia. Calf hypertrophy has been described in some patients. "Action" or grip myotonia may be seen. However, percussion myotonia is rare. There may be an associated neuropathy. EMG is the most valuable diagnostic test with continuous motor activity: spontaneous discharges, and rhythmical and continuous firing. The configuration of the wave forms varies, representing either motor units or single fiber discharges. Myokymia is seen electrically. This motor activity persists during sleep. Serum CK levels may be increased. No routine laboratory test is available to detect the antibodies which have been described in research studies. The diagnosis is made by the characteristic history of cramping and stiffness, which persists during sleep and the EMG findings of continuous spontaneous discharges and myokymia in the affected muscle groups. Sleep, narcosis and plexus block have no effect on the continuous motor activity, which can be blocked only succinylcholine. Plasma exchange can result in significant benefit, while the iv immunoglobulin can make symptoms worse. The differential diagnosis includes stiff-person syndrome (prominent muscle stiffness which disappears during sleep with no myokymia on EMG). Anti-GAD antibodies are found in stiff-person syndrome. Benzodiazepines are helpful in stiff-person syndrome, but have no effect in Isaacs syndrome. Phenytoin and carbamazepine are helpful for stiffness in Isaacs syndrome, while there is no effect in stiff-person syndrome. Another disease to be considered in the differential is the Schwartz-Jampel syndrome (myotonia, stiffness syndrome, dwarfism and muscle hypertrophy).

Other myokymia associated disorders: Are found in MS, polyneuropathy, lung cancer and thymoma with or without MG, pontine glioma and GBS. Serum autoantibodies to voltage-gated potassium channels (VGKC) (normal < 50 pmol/L) are found.

Hypothyroid myopathy: This consists of action myospasm and myokymia and of precussion myoedema and slowness of both contraction and relaxation phases of tendon reflexes. Serum CK levels are usually elevated. Although not true myotonia EMG may show myopathic pattern with bizarre high-frequency discharges. Biopsy is not very helpful.

Familial paroxysmal episodic ataxia (EA): EAs are unusual autosomal dominant disorders of early onset characterized by recurrent episodes of cerebellar ataxia. Most patients recover fully between attacks, but some may develop progressive ataxia with cerebellar atrophy. Stress, exercise and fatigue can trigger ataxic spells, which can respond dramatically to acetazolamide. Different types of EA have been identified: EA type 1, with myokymia and epilepsy, and attacks which usually last seconds to minutes, and may occur several times a day. Vertigo is present during episodes, but no nystagmus. Continuous myokymia between attacks are charateristic. Kinesigenic provocation (movement, startle or emotion) is common. EA1 is mapped to chromosome 12p13 and linked to mutations in KCNA1 (voltage-gated potassium channel gene). EMG shows continuous motor unit acitivity in all patients.; EA2 with interictal nystagmus, is long-lasting (hours) associated with attacks of vertigo, diffuse weakness, truncal and limb ataxia and downbeat nystagmus, often associated with nausea, vomiting and headache. The disease is often mistaken for MG. Provoking factors are stress, exercise and fatigue. EA2 is mapped to chromosome 19p13 and linked to mutations in CACNA1A (a calcium channel gene). The latter mutations have also been identified in familial hemiplegic migraine and SCA-6. Acetazolamide may be effective; paroxysmal choreoathetosis with EA, with attacks lasting for about 20 min and occurring at varying intervals.

Multifocal motor neuropathy with conduction block (MMN): This chronic idiopathic neuropathy may occur at any age (average 40) and presents usually as a slowly progressive asymmetrical distal limb weakness later on followed by muscle atrophy (may be accompanied by fasciculations, cramps and myokymia), but in the absence of spasticity, clonus, extensor plantars and pseudobulbar palsy. The disease usually begins and remains more prominent in the upper extremities. The first symptom is often inability to extend a single finger. The most striking clinical feature is the multifocal distribution of the weakness, which, in the beginning, may be localized within the territory of individual peripheral nerves. Loss of deep tendon reflexes is usually restricted to the affected areas. Sensation is essentially normal. CSF is normal. NCVs show a combination of multifocal motor conduction block (not the case in MND), prolonged or absent F- waves, prolonged distal latencies, reduced motor NCVs, or motor axonal loss with EMG evidence of denervation. Motor conduction block occurs most frequently in the ulnar and median nerves, both proximally and distally. But conduction block may be seen at any level of the peripheral nerve including the root, plexus, compression points (elbow for ulnar nerve, tibial head for peroneal nerve, etc.), or along a random segment. If parts of the nerve are not accessible for NCVs significant weakness in non-wasted muscles can substitute for it. A unique electrophysiologic feature of MMN is that sensory NCVs are typically normal, even across a segment of motor conduction block. The EMG in MMN typically shows evidence of axonal degeneration with fibrillation potentials and positive sharp waves in atrophic muscles. Sural nerve biopsies are either normal or show evidence of perivascular inflammation, demyelination, or reduced myelinated fiber density. Hence diagnostic criteria remain: 1) weakness w/o objective sensory deficit in the distribution of two or more named nerves (symptomatic asymmetric weakness; 2) definite conduction block in in two or more nerves outside common entrapment sites; 3)  normal sensory NCVs across the same segments, with demonstrated motor conduction block; 4) normal NCVs for min 3 nerves tested; 5) absence of pyramidal findings. Serum anti-GM1 myelin ganglioside, asialo-GM1, GM2, and GD1a IgM polyclonal antibodies are found in 1/3 of patients. High titer of IgM antibodies against GM1 identifies cases that are likely to respond to immunotherapy. Deterioration is steady or stepwise over years. The major differential diagnosis is PMA and ALS. Early in the disease course weakness is more pronounced than atrophy in affected muscles. This is an important clinical feature distinguishing MMN from MND, in which atrophy is generally consistent with the degree of weakness. Note that motor conduction block also occurs in compressive neuropathies, GBS, and CIDP. Human IV immunoglobulin (infused at a dose of 2 grams/kg in divided doses of 0.4 grams/kg on 5 consecutive days) is the treatment of choice. The onset of improvement occurred within 14 days, and the effects last approximately 2 months. Patients, therefore require frequent boosters to maintain their functional gains. Clinical improvement is not associated with a consistent decrease of anti-GM1 antibody titers and is not invariably accompanied by a reduction of motor conduction blocks. Steroids are ineffective and worsen the disease. Multifocal motor axonopathy (MMA) can present with asymmetric weakness and axonal electrophysiological features. It needs to be differentiated from LMN syndromes in particular adult progressive SMA. EMG and CSF help to distinguish MMN from CIDP and multifocal acquired demyelinating motor and sensory neuropathy. In contrast to CIDP, prednisolone and plasma exchange are ineffective. Iv immunoglobulin improve conduction block. Pregnancy may worsen MMN.

Strychnine poisoning: Strychnine is rapidly absorbed from the gastrointestinal tract, with symptoms developing within 10 to 20 minutes after ingestion. Acute encephalopathy (confusion) in association with episodes of muscle rigidity resulting in rhabdomyolysis is typical for strychnine poisoning. The initial symptoms of poisoning include nervousness, a hyperalert state, and acute confusion. Stiffness is first noted in the face and neck. Contraction of the facial muscles may cause risus sardonicus. The initial symptoms are soon followed by episodes of overwhelming muscle rigidity throughout the body in response to even minimal stimuli. Myokymia can be observed. Opisthotonos may be so severe that only the head and the heels touch the bed, with all voluntary muscles in full contraction resulting in rhabdomyolysis. The patient is fully conscious during the episodes, confirming the noncortical origin of the convulsions. In between the spasms, which last from 30 seconds to 2 minutes, the muscles become completely relaxed. During severe convulsions, there is respiratory arrest, and the combination of sustained muscle contraction and hypoventilation may result in rhabdomyolysis, myoglobinuria, and severe lactic acidosis. Without treatment, the patient usually dies from asphyxia and cardiac arrest after two to five such episodes. Most patients are treated with gastric lavage and instillation of charcoal at the first sign of poisoning. The spasms are usually treated effectively with benzodiazepines, phenobarbital, or pentobarbital. Occasionally, it is necessary to induce paralysis with pancuronium. Prophylactic endotracheal intubation and mechanical ventilation should be considered in cases of severe poisoning. Aggressive treatment with intravenous fluids may diminish the deleterious effects of myoglobinuria on the kidneys and improve the lactic acidosis. A variety of traditional remedies still exist, including coin rubbing, moxibustion, and the use of traditional herbs, aromatic oils, and teas. Strychnine, in the form of the nut of the Strychnos nux-vomica plant, is a traditional remedy in Cambodian. EEG is normal and EMG is not able to differentiate between generalized tetanus and strychnine poisoning. The diagnostic procedure is a test of the urine, gastric contents, or blood for strychnine.