Neuralgic amyotrophy (NA) is a distinct clinical entity that is characterized by attacks of sudden, severe neuropathic pain, followed within hours to days by a patchy paresis of several muscles in the distribution of branches of the brachial plexuses. Although most patients show slow signs of recovery in months to years many are left with persisting impairments. The disorder has both an idiopathic (INA) and hereditary form (HNA). The pathophysiological mechanism of INA and HNA is as yet unknown. The current hypothesis is that the attacks are caused by an auto-immune response. Management of patients will focus on alleviating the pain. Unfortunately, the initial pain hardly responses to any kind of analgesic. Current research focuses on indications that treatment in the acute stage with anti-inflammatory agents can abort the attacks and keep the damage to the peripheral nerves limited.
Authors
N. van Alfen, M.D. Ph.D.
B.G.M. van Engelen, M.D. Ph.D.
S. Geurts, M.D. Ph.D.
Clinical features
Neuralgic amyotrophy is characterized by attacks of sudden, severe neuropathic pain (painscore on a visual analogue scale often 8-10 out of 10), followed within hours to days by a patchy paresis of several muscles in the distribution of branches of one or both of the brachial plexuses. Sensory signs or symptoms are usually not very marked, although on careful examination patchy hypesthesia can be found in most patients. In the majority of patients, the right shoulder is affected, and the tell-tale sign of NA for most physicians is the conspicuous winging of the shoulder blade, the scapula alata. However, one of the major problems in prompt identification of the disorder is that the course and localization of both pain and paresis can vary considerably among patients, and even among recurrent attacks in one patient. Sometimes the only signs of an attack are a nasty pain in the upper arm lasting a few hours, and a subsequent inability to hold a pen or similar object, caused by a lesion of the anterior interosseus nerve. Read more
Natural course and prognosis
Because of this clinical variability, it is difficult to predict an individual patient his or her prognosis, unless the personal course and severity of the paresis are fully taken into account. Most textbooks say that after 2-3 years, over 95% of the patients will have recovered fully; however, our own experiences with both INA and HNA patients in the past 8 years have not been as hopeful. Although most people do show signs of recovery, and keep improving in the first 2-3 years after an attacks, many are left with persisting impairments or handicaps because they have not regained full strength or endurance of some muscle groups, or have shoulder joint instabilities and altered mobility which causes tendomyogenic pains. In a previous survey, 1/3 of patients with HNA were permanently unable to work because of their disorder.1
Epidemiology
In a recent large, prospective, community-based study in the London (UK) area, an incidence of 3 / 100.000 / year was found for INA.4 In the Netherlands, this translates to a minimun of roughly 400- 600 new patients each year. Probably the disorder is much more common once properly recognized.
It is thought that the disorder is slightly more common in men, but the patients' sex does not make the diagnosis more or less likely. The age of onset is usually in the second or third decade, but can vary from the neonatal age to the seventh decade. Patients with HNA tend to be younger when their first attack occurs (usually 2nd decade).
As for the caregivers, patients with NA are mainly seen by neurologists and/or orthopedic surgeons, but maybe even more frequently by physiotherapists, especially in the initial phase when the diagnosis has not yet been established.
Differential diagnosis
Because NA is still relatively unknown to many physicians, the initial diagnosis is very often thought to be a bursitis of the shoulder joint or a cervical radiculopathy caused by disk herniation. In our experience, the extremely severe pain in NA attacks reported by patients (as described above) is initially the best clue to establishing the correct diagnosis. This type of pain is very uncommon for a bursitis or even a cervical radiculopathy, in which the pain often depends on and fluctuates with the posture and activity of the affected limb. In addition, the pain in NA as a rule does not respond to analgesics or even opiates. Further in the course of the disorder, the clinical diagnosis can be made by a precise examination of the muscle groups affected. Read more
Ancillary investigations
In both INA and HNA laboratory investigations typically show no abnormalities. An exception can be the slight increase in cerebrospinal fluid protein content in some cases where lumbar puncture was performed. In 1/3 of the cases, the patient reports an antecedent (viral) infection or, rarer, another immunological event, such as vaccination, surgery or childbirth. NA has been associated with various preceding infections, but it is generally assumed that the damage is not caused by a direct infection of the plexus, but rather is due to a postinfectious auto-immune response involving the peripheral nervous system in a patchy way. Read more
Genetics
Hereditary neuralgic amyotrophy (OMIM 162100) is autosomal dominantly transmitted, with a high, but not complete, penetrance (estimated 60-80%). In a number of families with HNA the disorder has been linked to a region on chromosome 17q25.5 In some families mutatons in the SEPT9 gene have been found. There are also families in which the disease is not linked to this DNA region, so the disease must be heterogenous.
Therapy
Initially, the managament of patients will focus on alleviating the pain. For a succesful attempt at this, it is important to try and distinguish which pain type the patient has, or, put differently, in which stage of the attack he or she is. Unfortunately, as mentioned earlier, the initial severe pain hardly responses to any kind of analgesic, and the time for the effect of a co-analgesic (such as amitriptyline or gabapentin) to set in is usually a few weeks, by which time the pain may have already abated spontaneously. The only succesful intervention sofar has been the anecdotal use of corticosteroids in the acute phase, which seem to abort the attack by suppressing the (auto-) immune response. Read more
