Fundamentals of Neurology: An Illustrated Guide

10. Polyradiculopathy and Polyneuropathy




Image  Fundamentals

In this chapter, we will describe the characteristic syndromes produced by lesions affecting multiple nerve roots or peripheral nerves simultaneously (polyradiculopathy and polyneuropathy, respectively). If nerve roots andperipheral nerves are affected, the disorder is termed polyradiculoneuropathy. These very heterogeneous syndromes can be classified in various ways. Today, they are most commonly classified according to the following criteria:

Image Temporal course: polyradiculoneuropathy may present acutely with complete or partial remission, or itmay take a chronically recurrent or chronically progressive course.

Image Etiology: polyradiculoneuropathy may be of metabolic, endocrine, toxic, genetic/hereditary, infectious, inflammatory, autoimmune, or paraneoplastic origin.

Image Pathology: the functioning of the nerve roots and/orperipheral nerves may be impaired either by demyelination or by axonal degeneration. Slowing of nerveconduction early in the course of the illness is a distinguishing feature of demyelinating polyradiculoneuropathy.

The general manifestations of polyradiculopathic and polyneuropathic disorders include:

Image paresis,

Image diminution or absence of reflexes,

Image muscle atrophy,

Image sensory deficits and positive sensory phenomena (paresthesia, dysesthesia),

Image pain (in some patients),

Image predominantly distal symptoms and signs in a symmetrical distribution, or, in other patients, asymmetrical severity,

Image usually beginning in the lower limbs,

Image with more or less rapid progression,

Image with variable involvement of the autonomic nervous system.

The extent, severity, and distribution of these manifestations vary from patient to patient. In addition, predominantly radiculopathic processes are clinically distinguishable from exclusively neuropathic processes. These two types of illness are, therefore, presented separately in the following sections.

Image  Polyradiculitis

This term refers to an inflammatory process affecting many spinal nerve roots (most commonly the anterior ones), usually with simultaneous involvement of the proximal segments of the peripheral nerves. Inflammation of the nerve roots or nerves is usually not caused by infection, but rather by immune-mediated processes, e. g., an autoallergic radiculitis or neuritis following a prior, possibly asymptomatic viral or bacterial infection. Clinical variants of polyradiculitis are distinguished from one another by the degree of acuity and predominant localization of symptoms and signs. The acute form, Guillain–Barré syndrome, is the most common; the chronic form (CIDP = chronic inflammatory demyelinating polyradiculoneuropathy) is rarer, as is localized polyradiculoneuritis, which exclusively affect either the cranial nerves or the nerves of the cauda equina. Demyelinating processes are the main pathophysiological mechanism of polyradiculitis. Axonal degeneration is also present, to a varying degree, in CIDP, which explains its protracted course.

Classic Polyradiculitis (Landry–Guillain–Barré–Strohl Syndrome)

Acute polyradiculitis is characterized by rapidly ascending paresis, accompanied by at most 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. This illness, usually called Guillain– Barré syndrome for short, can appear at any age. Its annual incidence is between 0.5 and 2 cases per 100 000 persons. It tends to appear in the spring or fall.

Etiology and pathogenesis. This syndrome probably has more than one cause. Often, no precipitating factor can be identified. In some patients, the illness is preceded by Mycoplasma pneumonia or by infection with varicella-zoster virus, paramyxoviruses (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. Immunological processes play an important role in pathogenesis; in particular, there is an elevated concentration of antimy-elin antibodies. Finally, anti-GD1a antibodies are found in the rarer forms of the illness that involve axonal degeneration, but not in the more common, demyelinating forms (see above).


Fig. 10.1 Bilateral peripheral facial nerve palsy in Guillain–Barré polyradiculitis: a acute phase, b after recovery. (From: Mumenthaler, M.: Didaktischer Atlas der klinischen Neurologie, 2nd edn, Springer, Heidelberg, 1986.)

Clinical manifestations. The first sign is weakness of the lower limbs, beginning distally, occasionally some time after a preceding upper respiratory or gastrointestinal infection. There is no fever. Weakness ascends within a few hours or days, so that the patient becomes unable to walk. Distal paresthesiae and sensory disturbances are present in most patients, but are 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, as well as the muscles of the head and neck that are supplied by the cranial nerves. Dysphagia and bilateral facial palsy result (Fig. 10.1). Respiratory failure often develops rapidly and is a life-threatening condition requiring prompt treatment with intubation and artificial ventilation. In addition, involvement of the au-tonomic nervous system can cause life-threatening abnormalities of blood pressure regulation, cardiac rhythm, central respiratory drive, and, rarely, bladder function.

Diagnostic evaluation. The diagnosis is generally made from the clinical findings and confirmed by the characteristic finding of albumino-cytologic dissociation in the CSF. This term refers to an elevation of the CSF protein concentration without any accompanying elevation of the cell count; the finding may not be present, however, until two or three weeks after the onset of illness. Electrophysiological studiesusually reveal focal demyelination with conduction block, or, less commonly, axonal lesions.

Treatment. In severe cases, with profound weakness and rapidly progressive respiratory dysfunction, an intravenous infusion of immunoglobulins is indicated (0.4 g/kg body weight for five consecutive days). Another course can be given in four weeks, if necessary. Plasmapheresis, too, is effective and is recommended for all patients with rapidly ascending paresis and impending respiratory failure, even if the patient can still walk. Such patients should be hospitalized in an intensive care unit, so that their circulatory and respiratory function can be closely monitored and they can be intubated at once, if necessary. In milder cases, general supportive care often suffices: routine nursing, prophylaxis against venous thromboses, 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 (those that became weak first recover last). Recovery may take several months, however, or even up to two years in very severe cases. Most of the deaths caused by Guillain–Barré syndrome are complications of prolonged immobility (pneumonia, pulmonary embolism) or of autonomic dysfunction (respiratory failure, sudden cardiac death).

Chronic Inflammatory Demyelinating (Recurrent) Polyneuropathy (CIDP)

CIDP, a chronic form of polyradiculitis, has a similar pathophysiological mechanism to Guillain–Barré syndrome, the corresponding acute form. The weakness and autonomic dysfunction are usually less severe, but they last longer. The clinical manifestations fluctuate in severity, often taking a relapsing and remitting or chronically progressive course.

Pathogenesis. The idiopathic form of this condition is presumed to have an immunological 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 or systemic lupus erythematosus.

Clinical manifestations. CIDP differs from classic, benign Guillain–Barré polyradiculitis in the following ways:

Image chronic or relapsing-remitting course (more than four weeks),

Image possibly subacute course,

Image pain is common,

Image asymmetrical distribution of neurological deficits,

Image recurrent cranial nerve involvement,

Image marked elevation of CSF protein concentration, often combined with an elevated IgG index and pleocytosis,

Image central nervous manifestations are more common than in Guillain–Barré syndrome,

Image electroneurography reveals evidence of focal demyelination or axonal damage.

Diagnostic evaluation. Electrophysiological studies reveal slowing of nerve conduction, partial conduction blocks, and a delayed F wave.

Treatment. CIDP is treated with corticosteroids or immunosuppressive agents (cyclophosphamide) for a long period. Immunoglobulins and plasmapheresis are also used, sometimes in combination with immune suppression.


Although corticosteroids are indicated in the treatment of CIDP, they are only of questionable benefit in GuillainBarré syndrome.

Prognosis. The prognosis is unfavorable: 10% of patients die of the disease, 25 % remain severely disabled, and 5 to 10% have recurrences.

Multifocal Motor Neuropathy (MMN)

This is a special form of CIDP (see above).

Clinical manifestations. MMN is characterized by asymmetrical, slowly or rapidly progressive weakness with muscle atrophy and, sometimes, fasciculations (which may make MMN difficult to distinguish from ALS). There may also be dysarthria and sensory deficits. Some reflexes are lost.

Diagnostic evaluation. Electrophysiological studies reveal sporadic, circumscribed conduction blocks, and laboratory testing often reveals elevated anti-GM1 titers.

Treatment. MMN is treated like other forms of CIDP.

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, predominant, or only clinical manifestation of polyradiculitis. The differential diagnosis of such patients must always include borreliosis and chronic meningitis (p. 112).

Miller Fisher Syndrome

Clinical manifestations. This special form of cranial polyradiculitis, which mainly affects younger male patients, is characterized by

Image ophthalmoplegia,

Image ataxia, areflexia,

Image (sometimes) pupillary involvement (e. g., Adie pupil),

Image (sometimes) facial nerve palsy,

Image elevated CSF protein concentration,

Image (sometimes) accompanying brainstem signs.

Treatment. Miller Fisher syndrome has a favorable prognosis and generally needs no specific treatment.

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 and areflexia of the lower limbs and sphincter dysfunction. Many patients are presumably due to borreliosis or a herpes virus infection.



Polyneuropathy is a condition affecting multiple peripheral nerves, usually simultaneously, though possibly in more or less rapid sequence. The clinical manifestations are usually symmetrically distributed and slowly progressive. The first signs of polyneuropathy are practically always in the lower limbs. Its causes are many.

Etiology. The common causes of polyneuropathy are listed in Table 10.1.

Pathogenesis. A variety of harmful influences affect peripheral nerves in different ways and produce correspondingly different histopathological lesions. Initial damage of the neuronal nuclei, as in diabetes mellitus, leads to secondary, distal, retrograde axonal degeneration. On the other hand, primary damage to axons leads to Wallerian degeneration of the distal axon segments, as seen in many toxic polyneuropathies. The Schwann cells are another possible “target” of pathogenic influences, e.g., dysproteinemia. Loss of Schwann cells leads to demyelination.


General clinical manifestations. Polyneuropathy is usually characterized by:

Image first signs usually appearing distally in the lower limbs,

Image paresthesiae in the toes or soles of the feet, mainly at night,

Image tingling,

Image muffled sensation on the soles, “as if I had socks on,”

Image loss of the Achilles' reflexes,

Image diminution or loss of vibration sense, beginning distally.

Image as the condition progresses, there is paresis of the short toe extensors on the dorsum of the foot, as well as of the interossei (the patient can no longer spread his or her toes),

Image later, paresis of the long toe extensors and foot extensors,

Image producing bilateral foot drop,

Image finally, sensory disturbances and weakness spread to the upper limbs as well.

Diagnostic evaluation. When the typical clinical findings reveal the presence of polyneuropathy, a series of laboratory tests is performed to determine its etiology (particularly a complete blood count, electrolytes, glucose, CRP, electrophoresis, daily blood sugar profile, glucose tolerance test, HbAlc, renal and hepatic function tests, serum vitamin B12 and folic acid levels, vasculitis parameters, TSH, and perhaps further endocrine tests and tumor markers). Electroneurography reveals a variable degree of impairment of impulse conduction, depending on etiology. If the underlying lesion is primarily axonal, EMG reveals evidence of denervation or neuro-genically altered potentials. The CSF protein concentration is elevated in many types of polyneuropathy (e.g., diabetic polyneuropathy); in rare cases, CSF examination may yield evidence of an infectious process. Sural nerve biopsy is an additional means of distinguishing axonal from demyelinating forms of polyneuropathy, if the findings of ENG and EMG are inconclusive; it may also provide direct evidence of certain etiologies (e.g., vasculitis).

Particular Etiologic Types of Polyneuropathy

The types of polyneuropathy that are clinically most important, either because they are common or for other reasons, are described in the following sections.


Hereditary Motor and Sensory Neuropathies (HMSN)

The current classification of hereditary polyneuro-pathies is given in Table 10.2.

HMSN Type I (Charcot–Marie–Tooth disease) is the most common hereditary polyneuropathy, with a prevalence of two per 100 000 persons. It is genetically subdivided into Type Ia, caused by duplication on chromosome 17p11, and Type Ib, caused by a point mutation on chromosome 1q22–23. Clinically, its earliest manifestation is pes cavus (Fig. 10.2a), later followed by atrophy of the calf muscles, while the thigh muscles retain their normal bulk (“stork legs,” “inverted champagne-bottle sign,” Fig. 10.2). As the disease progresses, predominantly distal muscle atrophy is seen in the upper limbs as well (Fig. 10.2c). Distal sensory impairment may not arise until much later and even then is usually only mild. Electromyography reveals marked slowing of nerve conduction; histopathological examination of a sural nerve specimen reveals axonal degeneration, myelin changes, and onion-skinlike Schwann cells. HMSN Type I progresses very slowly. Patients can often keep working until the normal retirement age or beyond.

Hereditary neuropathy with predisposition to pressure palsies (HNPP) is an autosomal dominant disorder due to a point mutation in chromosome 17p11.2–12. Clinically, patients develop recurrent pressure palsies of individual peripheral nerves, even after very light pressure. The histopathological substrate of the disorder is an abnormality of the myelin sheaths of peripheral nerves. Microscopy reveals sausagelike, segmental swelling of the sheaths (“tomaculous neuropathy”).

Diabetic Polyneuropathy

Epidemiology. Diabetic polyneuropathy is the second most common type of polyneuropathy (only the alcohol-induced type is more common). It typically afflicts persons aged 60 to 70 who have suffered from diabetes for five to 10 years or more and 20 to 40% of diabetics have it to some degree. In 10% of patients with diabetic neuropathy, it is only the diagnostic evaluation of neuropathy that brings the underlying diabetes to light.


Fig. 10.2 Hereditary motor and sensory neuropathy (HMSN), type I (a and b) and type II (c). a Pes cavus. b Severe calf atrophy with normal muscle bulk in the thighs (“stork legs”). c Atrophy of the distal forearm muscles and of the intrinsic muscles of the hand. (From: Meier, C., Tackmann, W.: Die hereditären motorisch-sensiblen Neuropathien. Fortschr Neurol Psychiat 50:1982.)

Pathogenesis. Polyneuropathy is caused both by diabetic angiopathy and by the direct effect of elevated blood sugar. Axonal degeneration is usually the most prominent histological finding, though segmental demyelination sometimes predominates.

Clinical manifestations. Irritative sensory symptoms are most prominent at first, including paresthesia and, often, burning dysesthesia of the feet. Typically, Achilles reflexes are absent and there is a mainly distal impairment of touch and position sense. It is only later that about half of the affected patients develop motor deficits. The condition may present with an asymmetrical neurological deficit, or with isolated disease of an individual nerve, such as cranial nerves I–II, IV, and VI or the femoral n. Disturbances of autonomic innervation are also typical: dry, often reddened skin, bladder dysfunction, orthostatic hypotension, tachycardia, diarrhea, and impotence in young male diabetics. The effects of diabetes on the nervous system are listed in Table 10.3.

Treatment. Optimal glycemic control is of paramount importance. The pain of diabetic neuropathy, which is often severe, can be treated with carbamazepine, gabapentin, thioctic acid, clomipramine, or local capsaicin ointment. These drugs can also be combined with neuroleptic agents.

Toxic Polyneuropathies

The numerous substances that can cause a toxic poly-neuropathy will not all be listed here. We will merely illustrate the breadth of the clinical spectrum of toxic polyneuropathy by describing two very different, highly characteristic syndromes.

Though alcoholic polyneuropathy is very common, its pathogenesis is not fully understood. In addition to the direct effects of ethanol and acetaldehyde, alcoholics often suffer from nutritional deficiencies. Further contributing factors include possible defects of the enzymes alcohol dehydrogenase and acetaldehyde dehydro-genase. Clinically, intense pain in the lower limbs is often the most prominent symptom. Many patients also suffer from muscle cramps. The intrinsic muscle reflexes are diminished; Achilles reflexes are usually absent. Proprioception is impaired and touch and vibration sense are diminished distally. The calves are often tender to deep pressure. The dorsiflexors of the feet are weak. Motor conduction in the peroneal n. is slowed. The major finding of sural nerve biopsy is axonal degeneration.

Triaryl phosphate poisoning will serve here as an example of an acute toxic neuropathy whose manifestations can persist, either fully or in part. This substance is found in certain mineral oil derivatives used in industry. Their erroneous use as cooking oil leads to a clinical syndrome manifested at first by diarrhea and one to five weeks later by fever and other constitutional symptoms.

Tabele 10.3 Effects of diabetes mellitus on the nervous system



Special features


Central nervous system

cerebrovascular accidents spinal cord ischemia


Peripheral nervous system


distal, perhaps painful, symmetric, gradually worsening


Image sensorimotor

paresthesiae or burning pain in the feet, absent Achilles reflexes, diminished vibration sense, hypesthesia in a stocking distribution, occasional dorsiflexor weakness, occasional toe ulcers and joint destruction


Image proximal asymmetric

mainly affects lumbar plexus or femoral nerve, unilateral, acute, painful, weakness of hip flexors and quadriceps m., diminished knee-jerk reflexes, positive reverse Lasègue sign, hypesthesia in femoral n. distribution, occasional similar find ings in upper limbs, spontaneous improvement possible (as in mononeuropathy, see below)




Image CN III (most common)

painful, affects only extraocular muscles, regresses within a few months


Image other peripheral nerve

e. g., thoracic nerves with abdominal muscle weakness

Autonomic nervous system

bladder dysfunction

sphincter disturbance, atonic flaccid bladder



in younger male patients



chiefly at night


necrobiosis lipoidica

polycyclic cutaneous atrophy in women



particularly in the toes



particularly on the soles of the feet

Ten to 38 days after the exposure, flaccid paresis appears in the feet and then, within a few days, in all four limbs. Sensation is also impaired. In many patients, the deficits resolve only in part, or not at all, and spasticity of central origin frequently develops over the ensuing years. Histopathological examination reveals axonal lesions both in peripheral nerves and in the central nervous system.

Mononeuropathies and Mononeuritis Multiplex

Mononeuropathy is a neuropathy affecting a single peripheral nerve; mononeuritis multiplex is a type of peripheral neuropathy in which single nerves are affected one after the other, in a highly variable temporal sequence. As for their pathogenesis, most cases of these two entities are due to a vasculopathy, such as diabetic microangiopathy, polyarteritis nodosa, systemic lupus erythematosus, Sjögren syndrome, Wegener granulo-matosis, or atherosclerosis. Clinically, they are characterized by asymmetrically distributed weakness, sensory deficits, or autonomic dysfunction in the distribution of a single peripheral nerve, or, in later stages of mononeuritis multiplex, in the distribution of multiple peripheral nerves. Other manifestations of the underlying illness are usually present as well, e. g., constitutional symptoms such as fever, night sweats, and weight loss, an elevated erythrocyte sedimentation rate, and symptoms referable to the internal organs.