Peripheral nerve hyperexcitability is an umbrella diagnosis that includes (in order of severity of symptoms from least severe to most severe) Benign Fasciculation Syndrome, Cramp Fasciculation Syndrome, and neuromyotonia.



A bit about me

Hi, I’m Guy i’m 50 and live near Barnsley in the UK. I am married to Beverley and have 3 wonderfull kids and a Staffordshire bull terrier called Meg.

My PNH dissorder started over 6 years ago with a flu like onset after a virus, since then ive had no let up in my symptoms of muscle fasciculations (twitching), bad cramping, stiff muscles, fatigue, exercise intolerance, and now as time as gone on, neuropathic nerve pain in both lower legs.

I try and be as active as possible and manage to play competitive Crown Green Bowling all through the year. I’ve also managed to take my touring caravan and my family down to the South of France for the last 6 years. The only way to beat this condition is to continue with your life the best way you can.

About PNH

STATES OF PERSISTENT MUSCLE ACTIVITY

Introduction

This is a confusing group of clinical states, all characterized by some degree of regional continuous muscular activity that in some cases cannot be fully differentiated from one another. From a clinical perspective we have found it is useful to categorize them in groups that are caused by (1) hyperexcitability of the peripheral motor nerves (fasciculations and myokymia), (2) centrally mediated hyperexcitability of motor output (Isaac syndrome, stiff man syndrome), and (3) nonmyotonic hyperexcitability of muscle (rippling muscle disease, Schwartz-Jampel syndrome).

Hyperexcitability of Peripheral Nerve

This comprises a set of disorders in which peripheral motor nerve activity is augmented such that there are excessive, sometimes sustained contractions of the motor unit. Its mildest manifestation is benign fasciculation. In more severe form the manifestations include neuromyotonia, Isaacs disease, and a disease of potassium-gated ion channels (Morvan disease, or Morvan fibrillary chorea discussed below and in Chap. 54) that may also involve the brain. These processes are not generally familial and several lines of investigation suggest an acquired autoimmune nature (Newsom-Davis). For example, all but benign fasciculations are associated more often than might be expected with other autoimmune diseases such as myasthenia gravis and some respond to antiimmune therapies such as plasmapheresis, the patient’s serum possesses antibodies to either voltage-gated potassium channels as mentioned or, less frequently, to nicotinic acetylcholine (ACh) receptors (Vernino and Lennon).

Benign Fasciculations
A few random fasciculations in the muscles of the calf, small muscles of the hand or of the face, or elsewhere are seen in most normal individuals. They are of little significance but can be a source of worry to physicians and patients who have read that fasciculations are an early sign of amyotrophic lateral sclerosis. A simple clinical rule is that fasciculations in relaxed muscle are not indicative of motor system disease unless there is associated weakness, atrophy, or reflex change.

Healthy individuals experience intermittent twitching of a muscle (or even part of a muscle), such as one of the muscles of the thenar eminence, eyelids, calves, or orbicularis oculi. They may continue for days. Electromyographically, benign fasciculations tend to be more constant in location and more frequent and rhythmic than the ominous fasciculations of amyotrophic lateral sclerosis but such distinctions are not entirely reliable. Quantitative study of the motor unit size may be helpful in these circumstances by demonstrating normally modeled units in the benign form and abnormally large units because of reinnervation in the case of motor neuron disease (see Chap. 48).

Occasionally, benign fasciculations are widespread and may last for months or even years. In several of our patients they have recurred in bouts separated by months and lasting several weeks. No reflex changes, sensory loss, nerve conduction, EMG abnormality (other than fasciculations), or increase in serum muscle enzymes is found. Low energy and fatigability in some of these patients may suggest an endogenous depressive illness yet the fasciculations are not explained by this mechanism. Patients commonly report a sense that the muscles affected by the twitching are weak but this cannot be confirmed by testing and several of our patients, curiously most of whom have been physicians, complained of equally troubling migratory zones of paresthesias (Romero et al). Pain of aching or burning type may increase after activity and cease during rest. Fatigue and a sense of weakness are frequent complaints. We suspect that this fasciculatory state reflects a disease of the terminal motor nerves, for a few of our patients have shown slowing of distal latencies, and Coers and associates have found degeneration and regeneration of motor nerve terminals in similar cases. However, most such cases are of benign nature and settle down in a matter of weeks or months. In the cases reported by Hudson and colleagues, the condition, even after years, did not progress to spinal muscular atrophy, polyneuropathy, or amyotrophic lateral sclerosis. This conforms to our experience and to that reported from the Mayo Clinic where 121 patients with benign fasciculations, followed in some cases for more than 30 years, showed no progression of symptoms and did not acquire motor neuron disease or neuropathy (Blexrud et al). It should be acknowledged, however, that there are infrequent patients with seemingly benign fasciculations in whom the EMG shows some abnormal features (e.g., rare fibrillations) in numerous muscles and who later develop the other features of motor neuron disease. Carbamazepine, and to a lesser extent phenytoin, has been helpful in reducing the fasciculations and sensations of weakness in a proportion of cases and numerous other medications have been reportedly helpful.

Cramp-Fasciculation Syndrome
This is probably a variant of the aforementioned benign entity in which fasciculations are conjoined with cramps, stiffness, and systemic features such as exercise intolerance, fatigability, and muscle aches. Although affected individuals may be to some degree disabled by these symptoms, the prognosis is good. The salient finding on physiologic studies is that stimulation of peripheral nerves results in sustained muscle firing due to prolonged trains of action potentials in the distal motor nerve. This phenomenon may be brought out in special electrophysiologic testing, as described by Tahmoush and colleagues. In effect, this is a mild form of neuromyotonia, which is described further on. In a small number of patients with cramp-fasciculation syndrome it is possible to demonstrate the presence of autoantibodies directed against voltage-gated axonal potassium channels. Carbamazepine or gabapentin may be beneficial.

Continuous Muscle Fiber Activity (Isaacs Syndrome)
The relation of myokymia to the state called continuous muscle fiber activity is ambiguous. Sporadically in the neurologic literature there have been described patients whose muscles at some point begin to “work” continuously (see Isaacs). Terms such as neuromyotonia and widespread myokymia with delayed muscle relaxation are additional names that have been applied to what is essentially the same condition. At the moment, there is little reason to distinguish one from another except in gradations of severity. In each case the excessive and spontaneous activity can be attributed to hyperexcitability of terminal parts of motor nerve fiber, possibly as a result of a partial loss of motor innervation and compensatory collateral sprouting of surviving axons (Coers et al; Valli et al). Twitching, spasms, and rippling of muscles (myokymia) are evident, the latter being the main clinical sign. In advanced cases there is generalized muscle stiffness and a sense of weakness. Complaints of muscle aching are usual, but severe myalgia is uncommon. The tendon reflexes may be reduced or abolished. Any muscle group may be affected. The stiffness and slowness of movement make walking laborious (“armadillo” syndrome); in extreme cases, all voluntary movement is blocked. The muscle activity persists throughout sleep. Treatment: Phenytoin or carbamazepine often abolish the continuous muscular activity and cause a return of reflexes. Acetazolamide has been helpful in other cases (Celebisoy et al). Many of the idiopathic cases will improve spontaneously after several years, but plasma exchange may be tried if the symptoms are intractable.