Etiology
Metabolic
Diabetic amyotrophy
Diabetic amyotrophy affects approximately 1% of people with diabetes.[3] Although technically a radiculoplexopathy, it is the most common entity involving the lumbosacral plexus seen in clinical practice. Patients may have outright diabetes mellitus or glucose-intolerant states (e.g., prediabetes). The condition most likely has some component of immune-mediated microvasculitis and secondary nerve infarction.[3]
The condition initially presents with acute or subacute onset pelvic or thigh pain in a unilateral or asymmetric distribution. Pain is severe and patients may describe it as "boring." As the condition progresses, muscle weakness and atrophy develop, and the symptoms become bilateral. Pain may resolve (after 2 to 3 weeks) prior to onset of weakness and atrophy. Associated numbness, tingling and weight loss is common.[4]
Compressive
Compressive lumbosacral plexopathies
Neuropathies involving the lumbosacral plexus are uncommon but can mimic a mononeuropathy. Causes include compression from solid tumors, abscess, hematoma, or infiltrating malignancies.
Compressive lumbosacral radiculopathies
Although not typically thought of as a mononeuropathy, root lesions can mimic such disorders and need to be considered in the diagnosis. The lower nerve roots L5/S1 followed by L4/5 are most commonly affected. The most common causes are disk herniation and chronic degenerative changes. Metastatic tumors can also lead to acute nerve root compression and should be considered in a patient with a known primary malignancy.
Peroneal neuropathy
The most common mononeuropathy affecting the lower extremity, usually manifesting as foot drop.[5][6] Most often, the nerve is injured at the fibular neck due to compression (e.g., surgical positioning, crossing legs, or trauma).
The peroneal nerve is derived from the L4-S1 nerve roots. These fibers travel through the lumbosacral plexus and eventually the dorsal component of the sciatic nerve. Within the sciatic nerve, fibers of the common peroneal nerve run separately from the tibial fibers. Near the fibular neck, the common peroneal nerve divides into its terminal branches, the superficial and deep peroneal nerves.[1] Isolated deep peroneal neuropathies are less common.
Meralgia paresthetica
Due to compression of the lateral femoral cutaneous nerve. This nerve arises from the L2/L3 roots and travels around the pelvic brim, exiting anterior to the iliac spine before passing under the inguinal ligament. The lateral femoral cutaneous nerve provides cutaneous sensation over the anterolateral thigh.
Often seen in overweight people, but patients who wear tight-fitting clothes and workers using heavy tool belts are also at risk.
Morton neuroma (metatarsalgia)
This is a relatively common source of foot pain and is due to perineural fibrosis of an intermetatarsal nerve. Pain usually localizes to the base of the third and fourth toes.
Obturator neuropathy
Isolated obturator neuropathies are most commonly seen in women who have undergone obstetric/gynecologic procedures.
Sciatic neuropathy
The sciatic nerve arises from the L4-S2 nerve roots and lumbosacral plexus before exiting the pelvis through the greater sciatic foramen.[1]
Tibial neuropathy
The tibial nerve arises from the ventral division of the sciatic nerve and descends to the level of the medial malleolus, where it runs under the flexor retinaculum. The distal tibial nerve subsequently divides into 3 to 4 branches. The medial and lateral calcaneal sensory nerves are purely sensory and supply sensation to the heel of the foot. The medial and lateral plantar nerves contain both motor and sensory fibers that supply the medial and lateral sole, respectively. The tibial nerve is rarely involved in isolation. When involved, it usually occurs distally at the level of the ankle.[1]
Tarsal tunnel syndrome (distal tibial neuropathy)
Compression of the tibial nerve as it passes through the tarsal tunnel (flexor retinaculum, at the medial side of the ankle). It most frequently manifests as perimalleolar pain.[7]
Femoral mononeuropathy
The femoral nerve is derived from the lumbar plexus, which originates from the posterior divisions of the L2, L3, and L4 nerve roots.[1] This can result in weakness when walking and falls due to buckling of the knee.
Hereditary neuropathy with liability to pressure palsies (HNPP)
HNPP is a dominantly inherited but uncommon condition, secondary to PMP 22 deletion on chromosome 17.[8] It produces relapsing and remitting episodes of painless compression neuropathy at the common sites of entrapment (e.g., peroneal neuropathy at the fibular head).
Peripheral nerve injury
Injury to peripheral nerves is an important cause of compressive lower extremity mononeuropathies. Injury may be caused by trauma or surgery.
Infectious
Viral infections such as herpes zoster, HSV, EBV, and CMV can involve nerve roots, leading to a painful radiculitis. These are more commonly seen in people with altered immune function, such as older people or those with HIV. Patients can present with a mononeuritis multiplex pattern. HIV can also present in a mononeuritis multiplex pattern as well as a length-dependent sensorimotor polyneuropathy.
HIV
HIV infection is caused by a retrovirus that infects and replicates in human lymphocytes and macrophages. It erodes the integrity of the human immune system over time, culminating in immune incompetence and a susceptibility to infections and malignancy.
Herpes zoster
Caused by reactivation of a primary varicella zoster virus infection because of a decline in the virus-specific cell-mediated immunity. Usually presents with burning or stabbing pain followed by a vesicular rash in the affected dermatome. [Figure caption and citation for the preceding image starts]: Dermatome mapAdapted by BMJ from an image by Ralf Stephan [Citation ends].
Herpes simplex
Infection with HSV-1 or HSV-2 can cause oral, genital, and ocular ulcers. Most have unrecognized disease. Highly variable symptoms and signs range from tingling and burning with the eruption of vesicular lesions to painful ulcerations.
Epstein-Barr virus
Infectious mononucleosis is the clinical syndrome caused by EBV: characterized by fever, pharyngitis, lymphadenopathy, and atypical lymphocytosis in older children and young adults; often subclinical in young children.
EBV can cause a myriad of neurologic illnesses with or without the stigmata of infectious mononucleosis.[9]
Pain and weakness may indicate the presence of EBV radiculopathy, especially in immunocompromised patients.
Cytomegalovirus
CMV is a ubiquitous beta-herpes virus that infects most humans. In people with normal immune systems, CMV infection is often asymptomatic or manifested as infectious mononucleosis-like syndrome (fever, lymphadenopathy, and atypical lymphocytosis). In immunocompromised patients (patients with AIDS and transplant recipients), disease manifests with fever, bone marrow suppression, and tissue-invasive disease such as pneumonia, hepatitis, colitis, nephritis, and retinitis.
Pain and weakness may indicate the presence of CMV radiculopathy, especially in patients with AIDS.
Lyme disease
Lyme disease is caused by Borrelia infection. Patients can present with a mononeuritis multiplex or polyradicular pattern.
Leprosy
Leprosy is caused by Mycobacterium leprae.[10] It is uncommon in the developed world but can be considered in patients from an endemic area.
Antibiotic-associated
A nested case control found that current systemic use of fluoroquinolone antibiotics increased the risk of peripheral neuropathy by 47%, contributing an additional 2.4 cases per 10,000 patient-years of use.[11]
Inflammatory
Sarcoidosis
Etiology is unknown. However, several factors have been suggested, including genetic, immunologic, and infectious causes (e.g., viruses, Borrelia burgdorferi, Propionibacterium acnes, Mycobacterium tuberculosis, and Mycoplasma).[12]
Sjogren syndrome
Chronic inflammatory and autoimmune disorder characterized by diminished lacrimal and salivary gland secretion (sicca complex).[13] Etiology is unknown. There are few data concerning heritability or relative genetic risk. The greater prevalence in females has raised the possibility of estrogen and/or androgen deficiency playing a role in the etiology of this and other autoimmune diseases.
Rheumatoid arthritis
The most common inflammatory arthritis, characterized by symmetric arthritis of the small joints of the hands and feet. Etiology unknown, but genetic and infectious causes have been suggested.
Acquired demyelinating sensorimotor polyneuropathy
Presumed autoimmune etiology. Nerve biopsies from patients support the role of cell-mediated immunity. No clearly defined genetic or environmental risk factors.
Neoplastic-related
Malignancy can affect individual nerves, the plexus, and nerve roots in multiple ways.
Neoplastic compressive lumbosacral radiculopathy
Lumbosacral radiculopathy due to direct compression by a malignancy. Usually metastatic and can occur acutely. Should be considered in any patient with a known primary malignancy.
Neoplastic compressive lumbosacral plexopathy
Lumbosacral plexopathy due to direct compression by a malignancy. Mostly due to intra-abdominal extension, but growth from metastases is also possible.
Radiation-induced plexopathy
Radiation may give rise to localized ischemia and fibrosis because of microvascular insufficiency.
Lymphoma
Heterogeneous group of malignancies of the lymphoid system. Linked to infectious causes with bacteria and viruses, autoimmune disorders, immunodeficiency states, and environmental factors.
Amyloidosis
An amyloid protein deposition disease that may have a primary cause or be secondary to other diseases. It can be localized, systemic, inherited, senile systemic, or dialysis amyloidosis.
Paraneoplastic immune-mediated attacks
Tumor-induced autoimmunity against the nervous system can cause lumbosacral plexopathy.
Nerve sheath tumors
Range of tumors; neurofibrosarcoma is probably the most important life-threatening complication of neurofibromatosis type 1.
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