A few days after his return from a Caribbean holiday, a 23-year-old man developed mild flulike symptoms, including a sore throat and low-grade fever. He recovered from this illness completely. Several days later, however, he felt a mild tingling in his toes, and it seemed to him that his legs were weak. The next day, the weakness was so pronounced that he could only stand up from a sitting position by pushing himself up from the chair with his arms, and he had trouble walking as well. At first, he thought this weakness had something to do with his cold. A little while later, when he began to notice weakness in his arms as well; he panicked and presented himself to the emergency room of a nearby hospital.
The admitting physician examined him thoroughly, finding mainly proximal weakness of all four limbs. The intrinsic muscle reflexes were weakly elicitable. Sensation was intact, except for impaired vibration sense on the feet and calves. The patient had no difficulty urinating.
The rapid development of mainly proximal, flaccid weakness of all four limbs (quadriparesis) with only mild sensory impairment and intact micturition is characteristic of Guillain–Barré syndrome (GBS). This disease is often associated with a prior upper respiratory or gastrointestinal infection; autoimmune processes play a role its pathogenesis. The cause of GBS remains unclear in most cases (idiopathic GBS). Treatment with immunoglobulins or plasmapheresis lessens the severity of the disease and accelerates the resolution of weakness.
This patient had had a mild cold before the neurologic deficits set in. As he had always been healthy up to that point, the doctors presumed he had idiopathic GBS. They nonetheless tested him for HIV, for the sake of completeness.
Three days after admission, the doctors were surprised by a laboratory report of a positive HIV test. There had been nothing in the history or the physical findings to arouse suspicion of an HIV infection. On repeated questioning, the patient said he had, in fact, had unprotected sexual intercourse on multiple occasions.
HIV infection rarely presents with acute polyradiculitis, as in this case. Thus, this patient had a type of symptomatic rather than idiopathic GBS. Like idiopathic GBS, this form of the disease is treated with immunoglobulins; antiretroviral drugs are given at the same time. The prognosis of HIV-associated GBS, like that of other forms of the disease, is favorable.
On discharge to a rehabilitation hospital 2 weeks later, the patient’s muscular strength had already markedly improved. He regained full strength during a brief rehabilitation period. He tolerated antiretroviral therapy without any further problems.
In this chapter, we will describe the characteristic syndromes produced by lesions that affect multiple nerve roots or peripheral nerves simultaneously (polyradiculopathy and polyneuropathy, respectively). If nerve roots and peripheral nerves are affected, the disorder is termed polyradiculoneuropathy.
Classification These very heterogeneous syndromes can be classified in various ways. Today, they are most commonly classified by the following criteria:
Temporal course: polyradiculoneuropathy may present acutely with complete or partial remission, or it may take a chronically recurrent or chronically progressive course.
Localization: symmetric versus asymmetric, distal versus proximal, lower or upper limbs affected versus lower and upper limbs affected, involvement of a few individual nerves (mononeuropathy multiplex).
Etiology: polyradiculoneuropathy may be of metabolic, endocrine, toxic, genetic/hereditary, infectious, inflammatory, autoimmune, or paraneoplastic origin.
Pathology: the functioning of the nerve roots and/or peripheral nerves may be impaired either by demyelination or by axon degeneration. Different types of nerve fibers may be affected (e.g., motor vs. sensory, large fibers vs. small fibers). Slowing of nerve conduction (or conduction block) early in the course of the illness is a distinguishing feature of demyelinating polyradiculoneuropathy, as opposed to diseases that involve axon degeneration.
General clinical features Polyradiculopathy and polyneuropathy are characterized by:
Weak or absent reflexes.
Sensory deficits and positive sensory phenomena (paresthesia, dysesthesia), with or without pain.
Mainly distal manifestations in a symmetric distribution (rarely, asymmetric).
Usually beginning in the lower limbs.
With more or less rapid progression.
With variable involvement of the autonomic nervous system.
The extent, severity, and distribution of these manifestations vary from patient to patient. In particular, mainly radiculopathic processes are clinically distinguishable from exclusively neuropathic processes. These two types of process are, therefore, presented separately in what follows.
This term refers to an inflammatory process that affects many spinal nerve roots (most commonly the anterior ones), usually with simultaneous involvement of the proximal segments of the peripheral nerves. The cause of the inflammation is sometimes a direct infection, but more often an autoimmune reaction. Clinical variants of polyradiculitis are distinguished from one another by the temporal course and predominant localization of the inflammation. The acute form, GBS, is more common; the chronic form (chronic inflammatory demyelinating polyradiculoneuropathy [CIDP]) is rarer.
Another rare form is localized polyradiculoneuritis exclusively affecting either the cranial nerves or the cauda equina.
In most cases, the inflammation is not directly due to an infection, but rather due to an autoimmune-mediated process, that is, an autoallergic radiculitis/neuritis following a viral or bacterial infection (which may be subclinical).
Demyelination is the main pathophysiologic mechanism of autoimmune polyradiculitis. Axon degeneration is also present, to a varying degree, in CIDP, which explains its protracted course.
11.2.1 Guillain–Barré Syndrome
GBS (also called Landry–Guillain–Barré syndrome) is the classic example of a polyradiculitis.
Acute polyradiculitis is characterized by rapidly ascending paresis and only mild sensory disturbances. In severe cases, the cranial nerves and autonomic system can be involved. Weakness usually improves spontaneously in all involved muscles; those that became weak first recover last. The prognosis is favorable.
Epidemiology GBS can strike at any age. Its incidence is from 0.5 to 2 cases per 100,000 persons per year. It tends to appear in the spring or fall.
Etiology and pathogenesis This syndrome has more than one cause, and the etiology often remains unclear. In some patients, the illness is preceded by Mycoplasma pneumonia or by infection with varicella zoster virus (chickenpox), paramyxovirus (mumps), HIV, Epstein–Barr virus (infectious mononucleosis), or Campylobacter jejuni. The last-named organism often produces axonal lesions and is associated with a particularly severe form of the illness. Immunologic processes play an important role in pathogenesis; in particular, antimyelin antibodies are often found. Anti-GD1a antibodies are sometimes found in the rarer forms of the illness that involve axon degeneration, but not in the more common, demyelinating forms (see earlier).
Clinical features The first sign is weakness of the lower limbs, beginning distally, occasionally in the aftermath of an upper respiratory or gastrointestinal infection. There is no fever. Weakness ascends within a few hours or days, and the patient may become unable to walk. Distal paresthesiae and sensory disturbances are usually present, but much less disturbing to the patient than the weakness. Though the weakness ascends rapidly, its ultimate extent is variable. In very severe cases, the upper limbs, diaphragm, and accessory muscles of respiration are affected within a few days of onset, as well as the muscles of the head and neck that are supplied by the cranial nerves. Inability to swallow and bilateral facial palsy ensue ( ▶ Fig. 11.1). Life-threatening respiratory failure often develops very rapidly. In addition, possible involvement of the autonomic nervous system can cause life-threatening abnormalities of blood pressure regulation, cardiac rhythm, central respiratory drive, and, less commonly, bladder function.
Fig. 11.1 Bilateral peripheral facial nerve palsy in Guillain–Barré polyradiculitis. a Acute phase. b After recovery.
Diagnostic evaluation The diagnosis is generally made from the clinical findings and confirmed by the characteristic finding of albuminocytologic dissociation in the cerebrospinal fluid (CSF), classically described in 1916 by Guillain, Barré, and Strohl: the CSF protein concentration is elevated, without any accompanying elevation of the cell count. This finding may not be present, however, until 2 or 3 weeks after the onset of illness. Electrophysiologic testing usually reveals focal demyelination with conduction block, or, less commonly, axonal lesions.
Treatment In mild cases, general supportive care is all that is needed, with close monitoring of muscle strength and vital capacity. In severe cases, with profound weakness and rapidly progressive respiratory dysfunction, the intravenous infusion of immunoglobulins is indicated (0.4 g/kg body weight daily for 5 consecutive days). A second course of treatment can be given 4 weeks later if necessary. Plasmapheresis is an effective alternative, for example, for patients with contraindications to immunoglobulin therapy. Patients with rapidly ascending paresis and impending respiratory failure must be hospitalized in an intensive care unit, so that their circulatory and respiratory functions can be closely monitored and they can be intubated without delay, if necessary. Cardiac complications and pain are treated symptomatically.
Patients with dysphagia are fed through a nasogastric or gastrostomy tube. Other important elements of care are: prophylaxis against deep venous thrombosis (and pulmonary embolism), urinary catheterization if needed, and, later, physical therapy.
Prognosis The prognosis is generally favorable. Intensive care may be needed in the acute phase, but, once this is past, the weakness usually resolves in all affected muscles. The muscles that were weak first recover last. Recovery may take several months, however, or even up to 2 years in very severe cases. Permanent, mainly distal muscle atrophy is not uncommon. Most of the deaths caused by GBS are attributable to prolonged immobility (pneumonia, pulmonary embolism) or autonomic dysfunction (respiratory failure, sudden cardiac death). Death from this disease is rare in the current era of intensive care and complication prevention.
11.2.2 Chronic Inflammatory Demyelinating (Recurrent) Polyneuropathy
CIDP, the chronic variant of polyradiculitis, is pathophysiologically similar to the acute variant (GBS, see section ▶ 11.2.1). It develops over a period of 8 weeks or more. The weakness and autonomic dysfunction are usually less severe than in GBS, but they last longer.
Pathogenesis The idiopathic form of this condition is presumed to have an autoimmune basis. Immunoglobulins are found in the CSF, and immunoglobulin deposits are seen in biopsy specimens of the sural nerve. There are also forms of CIDP associated with HIV and systemic lupus erythematosus.
Clinical features CIDP differs most obviously from classic, benign Guillain–Barré polyradiculitis in its slower course. Its main clinical features are:
Chronic or relapsing–remitting course (at least 8 weeks).
(Possibly) subacute course.
Symmetric or asymmetric distribution of neurologic deficits.
Recurrent cranial nerve involvement.
Central nervous manifestations are more common than in GBS.
Electroneurography (ENG) reveals evidence of focal demyelination or axonal involvement.
Marked elevation of CSF protein concentration, often combined with an elevated immunoglobulin G index, while the cell count is normal.
Fluctuation of the signs and symptoms is also typical: there may be phases of complete remission followed by relapse, or else the manifestations may progress slowly over a long period of time.
Diagnostic evaluation ENG reveals slowed nerve conduction, partial conduction blocks, and a delayed or absent F wave. In cases with axonal involvement, electromyography (EMG) reveals low-amplitude summed muscle potentials and abnormal spontaneous muscle activity.
Treatment CIDP can be treated effectively with corticosteroids and immunoglobulins and with plasmapheresis. Depending on the response, long-term treatment may be needed, either with immunoglobulins or with immunosuppressive drugs (corticosteroids, azathioprine, cyclophosphamide).
Corticosteroids are indicated to treat CIDP, but not GBS.
Prognosis CIDP takes either a relapsing–remitting or a chronic progressive course; the former carries a better prognosis. More than half of all patients need long-term treatment.
Multifocal Motor Neuropathy
Multifocal motor neuropathy (MMN) is a special variant of CIDP.
Clinical features MMN is characterized by asymmetric, slowly or rapidly progressive weakness with muscle atrophy and, sometimes, fasciculations (which may make MMN hard to distinguish from amyotrophic lateral sclerosis). There may also be dysarthria and sensory deficits. Some reflexes are lost.
Diagnostic evaluation The key diagnostic finding in ENG is that of sporadic, circumscribed nerve conduction blocks. Laboratory testing often reveals elevated anti-GM1 titers.
Treatment MMN is treated like other forms of CIDP.
11.2.3 Cranial Polyradiculitis
Polyradiculitis of the cranial nerves may be a component of ascending polyradiculitis, in which case it generally arises only after the limbs have become paretic. Sometimes, however, it is the first, main, or only clinical manifestation of polyradiculitis.
The differential diagnosis of patients with cranial polyradiculitis must always include borreliosis and chronic meningitis (see section ▶ 6.7.4).
Miller Fisher Syndrome
Miller Fisher syndrome is a variant of cranial polyradiculitis that mainly affects young men. It is presumed to share a pathogenesis with Bickerstaff encephalitis, in which brain stem involvement predominates.
Clinical features Miller Fisher syndrome is characterized by the following:
(Sometimes) facial nerve palsy ( ▶ Fig. 11.1).
(sometimes) accompanying brainstem signs.
Electrophysiologic evidence of a sensory axonal neuropathy.
Diagnostic evaluation The diagnosis rests on the typical clinical features and the serologic demonstration of antiganglioside antibodies GQ1a and b. The CSF protein concentration is elevated.
Treatment Miller Fisher syndrome has a favorable prognosis and generally needs no specific treatment.
11.2.4 Polyradiculitis of the Cauda Equina
This rare type of polyradiculitis, also called Elsberg syndrome, is characterized by isolated involvement of the sacral roots, producing distal weakness, areflexia of the lower limbs, and sphincter dysfunction. Many cases are presumably due to borreliosis or a type 2 herpes virus infection.