Porphyrias

Porphyrias are a group of metabolic disorders characterized by defects in the synthesis of heme, a metalloporphyrin that is the product of porphyrin metabolism. Presentation of the disorder typically involves abdominal pain, vomiting, constipation, hypertension, tachycardia, photosensitivity, psychosis, and neuropathy. Neuropathy is estimated to affect 10% to 40% of patients and is primarily motor (126). Cranial neuropathies have been described but facial paralysis is rare (127). Although the mechanism of neuropathy is unknown, several autopsy as well as biopsy studies have implicated a distal axonal lesion (128). Investigators have hypothesized that some of the abnormally elevated heme byproducts, such as delta-aminolevulinic acid, may have a direct neurotoxic effect. Alternatively, heme deficiency in neural tissue may be cytotoxic or may lead to neurotransmitter dysfunction. Diagnosis is confirmed by identifying a markedly increased urinary porphobilinogen level. Treatment of an acute attack involves intravenous hemin therapy started as soon as possible. Intravenous glucose alone is appropriate only for mild attacks or until hemin is available. The prognosis for recovery of facial neuropathy is variable, but typically, recovery is slow over many months and often with incomplete return of function or residual synkinesis. Repeated attacks usually lead to progressive dysfunction with the ultimate long-term prognosis dependent on the ability to adequately prophylax against recurrence of the attacks (126).

Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder with antibodies directed at the postsynaptic receptors for the neurotransmitter acetylcholine. As the receptors are destroyed, the axonal nerve signals cannot be communicated to the muscles, resulting in progressive muscle fatigue and paralysis. Typical presentation is ocular weakness including ptosis and ophthalmoplegia and is present in 90% of the cases. The facial nerve can be involved with myasthenia gravis and can be unilateral or bilateral of varying severity (129,130). In rare cases, the facial nerve can even be involved without any ocular weakness (131). Diagnosis can be made by giving a test dose of edrophonium, because patients with myasthenia gravis show dramatic improvement in muscle weakness after intravenous infusion. Finding antibodies to the acetylcholine receptor in the serum is diagnostic. Treatment consists of anticholinesterase inhibitors that prevent the breakdown of acetylcholine at the neurosynaptic junction providing more availability of this neurotransmitter to function on the reduced numbers of receptors available. As with other muscle weakness found in this disorder, the facial nerve function dramatically improves with neostigmine or other anticholinesterase inhibitors.

Hypothyroidism

Thyroid hormone plays a critical role in regulating metabolism. In hypothyroidism, the basal metabolic rate is decreased due to a lack of thyroid hormone, resulting in bradycardia, cold intolerance, alopecia, and weight gain. Neurologic symptoms are relatively common in hypothyroidism and include paresthesias in up to 80% of patients as well as ataxia, coma, headache, seizure, cerebellar signs, and psychosis (132,133). Cranial nerve involvement has also been reported, with the vestibulocochlear nerve most commonly affected in 15% to 31% of patients with hypothyroidism (132). Involvement of the facial nerve is considered rare. Its mechanism is thought to be a compressive phenomenon. In hypothyroidism, myxedematous infiltration and swelling of the soft tissue are hypothesized to have a compressive effect on the facial nerve through the tight confines of the fallopian canal. Anecdotal reports of facial nerve decompression in hypothyroidism have been described (134), but additional reports state that the facial paralysis resolves as the thyroid abnormality is corrected (133). Treatment involves thyroid hormone supplementation.

Diabetes Mellitus

Diabetes mellitus results from a lack of insulin production causing an elevated level of serum glucose. The presentation ranges from asymptomatic to ketotic coma. Neurologic

TABLE 2 Malignant Hypertension and Facial Paralysis Review

Investigator

Year

Patients with malignant HTN

Patients with facial involvement (percentage)

1956 1966 1929 1974 1982

79 35 25 70 45 254

7 (8.9%), 6 (17.1%) 2 (8%) 2 (2.9%) 2 (4.4%) 19 (7.5%)

Amberg (142) Rance (143) Trompeter (144) Totals

1929-1982

Abbreviation: HTN, hypertension.

sequelae are quite common and most often are seen as a peripheral neuropathy in the lower legs. The incidence of facial neuropathy in diabetic patients has been estimated between 0.5% and 2.5% without a clear link to blood glucose control (135,136). This incidence of facial involvement is elevated when compared to the incidence of facial paralysis in the general population of 0.1%. In fact, Korzyn reported that among 130 cases studied of facial palsy, 20% had diabetes with as many as 66% demonstrating impaired glucose tolerance (137).

The primary systemic effects are caused by injury to the microvascular blood supply from the elevated serum glucose levels that result in impaired microvascular circulation. The blood supply to the facial nerve can be affected by diabetes resulting in facial paralysis that can be temporary or permanent. The most susceptible area of the facial nerve to vascular compromise is the labyrinthine segment, a watershed area where the carotid and vertebrobasilar systems connect. Treatment involves aggressive control of blood sugars with frequent monitoring of glucose levels. Corticosteroid therapy for facial nerve dysfunction is contraindicated, as glucocorticoids result in a substantial elevation of serum glucose.

Malignant Hypertension

Moxon first reported hypertension as a cause of facial paralysis in 1869 (138). Since that time, an association between peripheral facial paralysis and hypertension has been confirmed. Paine reported on 80 pediatric cases presenting with facial palsy over a seven-year period at Boston's Children's Hospital and found two cases (2.5%) resulted from malignant hypertension (139). This link is substantiated by a review of the literature on pediatric malignant hypertension, which reveals a consistent incidence of facial nerve involvement ranging from 3% to 17% (Table 2).

An association between malignant hypertension and peripheral facial paralysis in adults has also been found. In a review by Clarke of 190 patients with malignant hypertension, 38% were found to have various neurologic sequelae including focal brain ischemia, cerebral hemorrhage, subarachnoid hemorrhage, hypertensive encephalopathy, mental disturbances, convulsions, and cranial neuropathies. The facial nerve was the most common cranial nerve involved with an incidence of 10% for isolated facial nerve involvement in adults with malignant hypertension (140).

The pathogenesis of the lower motor nerve involvement of the facial nerve may be from recurrent hemorrhage within the facial canal. This theory has been supported by two autopsies where blood clots were identified within the facial canal (138,141). Alternatively, edema of the nerve with compression of the blood supply could cause the paralysis.

The prognosis for facial nerve recovery is quite good with treatment aimed at correcting the hypertensive state (145). An anecdotal report of facial nerve decompression in a patient with hypertension as the etiology resulted in complete return of facial nerve function (146). However, given the excellent outcome without surgery, many advocate a more conservative approach. Glucocorticoid therapy is contraindicated as this may exacerbate the hypertensive state (147). Investigators now stress the need to measure blood pressure in any child presenting with facial paralysis (148).

Pregnancy

An increased risk of acute facial paralysis has been noted in pregnancy dating as far back as Sir Charles Bell in his 1830 publication (149). Pregnant women have a 3.3-fold increased risk for facial paralysis when compared to age-matched nonpregnant women (149). Timing of the facial paralysis during pregnancy is as follows: 5% in the first trimester, 6% in the second trimester, 71% in the third trimester, and 18% within one week postpartum (150). Of the cases, 35% had incomplete paralysis with 65% of cases demonstrating complete paralysis within 10 days of its onset. An increased risk for facial paralysis was also correlated with preeclampsia with a sixfold increased risk identified (151).

There are many possible mechanisms for facial nerve involvement in pregnancy. Elevated progesterone levels are known to cause an increase in extracellular fluid content, which could result in edema and injury to the facial nerve along its tight bony course within the temporal bone (152). This might explain the increased incidence of facial paralysis in the third trimester, when progesterone levels are at their highest.

Viral inflammation or immunosuppression during pregnancy is the alternative explanation (153). Naib demonstrated that the incidence of herpes simplex in pregnant women is higher than in nonpregnant women. Gestational immunosuppression from rising cortisol levels is well known and may then lead to viral reactivation. In terms of prognosis, no effect or correlation of facial involvement was identified on neonatal outcome (151). For incomplete paralysis, all patients demonstrated complete recovery. For the pregnant women demonstrating complete facial paralysis, only 52% achieved satisfactory outcome. This is statistically significant when compared to aged-matched nonpregnant women as well as men with Bell's palsy, who achieved 77% to 88% incidence of satisfactory outcome (House Brackman I or II). Corticosteroid therapy did not appear to alter the outcome. One author has advocated induction of delivery early in the last week of pregnancy followed by facial nerve decompression (154).

Vaccinations

In 1999, a review of 1526 patients in Switzerland, who were given the intranasal influenzae vaccine, found 11 cases of facial paralysis ranging from 3 to 43 days after the vaccination was administered, yielding an incidence of 0.7%. The intranasal influenzae vaccine is a virosomal vaccine that also contains adjuvant heat-labile Escherichia coli toxin. The facial paralysis resolved in 10 of 11 patients. When compared to the spontaneous incidence of 0.02% in this patient population, this was considered a significant increase in the incidence of facial paralysis and the intranasal influenzae vaccine was removed from the market. Since that time, a second intranasal influenzae vaccination has been introduced based on live attenuated cold-adapted influenzae virus, without any cases of facial paralysis (155).

Additional investigations have been performed for parenteral influenza vaccines. Using the vaccine adverse event reporting system in the United States for the years 1991— 2001, a total of 197 reports of facial paralysis were documented after injection of influenza vaccines. The study compared the incidence of facial paralysis with influenza vaccine to the incidence of facial paralysis to other vaccines and concluded a "possible association between influenza vaccines and increased risk of Bell's palsy" (156).

A study of the incidence of facial paralysis after hepatitis B vaccination revealed 10 cases over a three-year period with 850,000 vaccines administered. Analysis found that this was not an increase over the expected incidence of Bell's palsy but did find an association with Guillain-Barre syndrome, with five cases documented over the same three-year time period (157).

Toxicity

Toxic exposures have, on rare occasions, resulted in facial paralysis. Ethylene glycol, or antifreeze, has resulted in unilateral and bilateral facial paralysis when ingested. Patients who have ingested glycol also have ataxia, dysarthria, and visual changes (158). Arsenic intoxication has also been linked with facial paralysis. A single case report of neurologic and gastrointestinal disturbances presenting as facial paralysis and pancreatitis following arsenic intoxication was described in a literature review (159). Chronic arsenic toxicity is known to cause a symmetric polyneuropathy of sensory and motor nerves, but cranial nerve involvement is rare. Lithium toxicity has also been reported to cause facial nerve involvement (160). Chronic alcohol intoxication was hypothesized as the cause of bilateral facial paralysis in a patient with Wernicke-Korsakoff syndrome (158).

Some chemotherapeutic agents have been linked with facial nerve involvement. Paclitaxel has been reported to cause bilateral facial paralysis after only a single cycle (161).

Embolization for Epistaxis

Arterial embolization has been used to treat recalcitrant epistaxis since 1974 (162). Since that time, a literature review reveals 13 cases of facial paralysis after embolization of branches of the external carotid artery. The majority occurred immediately after embolization, with most of the others occurring within the first hour after embolization (163). In one case after bilateral middle meningeal artery ligation, a patient developed bilateral facial paralysis within 36 hours of embolization, which lasted five months before the patient demonstrated full recovery (164).

Facial nerve paralysis occurred using both absorbable and nonabsorbable materials for the embolization (163). Complete recovery of the facial nerve occurred in only 40% of the cases.

Theories about the pathogenesis of injury are related to the major blood vessels that supply the facial nerve along its course. The internal auditory artery is a branch of the AICA coming from the basilar artery and supplies the portion of the nerve running within the IAC. The petrosal artery is a branch of the middle meningeal artery coming from the internal maxillary artery and supplies the labyrinthine and horizontal segments of the facial nerve. Finally, the stylomastoid artery is a branch of either the occipital artery or the posterior auricular artery and supplies the vertical portion of the facial nerve.

A detailed discussion of epistaxis can be found in Chapter 31.

SYSTEMIC NEOPLASMS Leukemia

Leukemia represents a hematogenous malignancy of the white blood cells. Four different subtypes exist: acute myelogenous leukemia (AML), chronic myelogenous leukemia, acute lymphomatoic leukemia, and chronic lymphomatoid leukemia. These diseases are discussed in detail in Chapter 17.

Presentation varies dramatically depending on the subtype, but patients usually suffer from inadequate hematopoietic production of precursor cells due to leukemic infiltration of the bone marrow. Infections, bleeding, pallor, lethargy, malaise, and fever are frequent symptoms (165). Diagnosis is confirmed with characteristic elevation of the white-blood cell count and diagnostic finding on bone marrow biopsy. Extramedullary disease occurs, most often involving the central nervous system and testes (165). An uncommon manifestation of myelogenous leukemias is the chloroma, also known as a granulocytic sarcoma or myeloblastoma, occurring in roughly 5% of patients with AML (166). Chloromas represent a focal deposition, or mass, comprised of immature myeloid cells. Chloromas can be found in any location.

Temporal bone involvement has been found in 36% of temporal bones evaluated in leukemic patients (167). Facial nerve paralysis has been associated with leukemia but is considered unusual (168). Facial nerve involvement is most often seen with meningeal leukemia with involvement of the facial motor nucleus (167). Less commonly, direct invasion of leukemic cells, such as a chloroma along any portion of the course of the facial nerve, including the parotid gland, can lead to facial nerve dysfunction (169,170). The leukemic invasion involves the perineurium, and to a lesser extent, the endoneurium (167). Treatment involves chemotherapy with focal radiation therapy at the site of the chloroma. When the chloroma involves the mastoid bone, surgical treatment is restricted to obtaining a biopsy for diagnosis, and recovery occurs without decompression of the facial nerve (171).

Lymphoma

Lymphoma represents a malignancy of the lymphoreticular epithelial system. It is generally divided into Hodgkin's and non-Hodgkin's lymphoma. This is discussed further in Chapter 17. Although the presenting systems are quite variable, lymphadenopathy is usually a prominent feature. Patients may also develop fatigue and night sweats. Non-Hodgkin' s lymphoma more commonly involves extranodal sites. Lymphoma can involve the temporal bone either primarily or from metastatic disease.

When facial nerve involvement occurs, it is usually from direct involvement of the lymphoma along the course of the facial nerve. It is considered an exceptionally rare complication of lymphoma (172) but is well described (173-176). Tucci reports two cases of primary lymphoma of the temporal bone which presented with facial paresis (174). In both cases, the facial paresis recovered completely after chemotherapeutic treatment was given. Metastatic involvement of the temporal bone is much more common than primary lymphoma involvement. Treatment depends on the type of lymphoma but is primarily multidrug chemotherapy. Facial paralysis involved with temporal bone lymphoma usually follows the course of the disease (175).

Multiple Myeloma

Multiple myeloma, also known as myeloma or plasma cell myeloma, is a hematogenous malignancy of the plasma cells. It is the second most common hematogenous malignancy behind non-Hodgkin' s lymphoma. Patients early in the disease are often asymptomatic but later can develop lower back and rib pain as well as anemia and kidney dysfunction. Diagnosis is confirmed by the presence of excess protein (so-called M protein) in the blood or urine and an increased number of plasma cells on bone marrow biopsy.

The first case of multiple myeloma of the temporal bone was published in 1979 by Lavine. Shone documented the first case of facial involvement with multiple myeloma in 1985 (177), with other investigators presenting similar cases (178-180). Temporal bone histopathology in multiple myeloma patients has shown a high percentage of involvement, with 87% of bones examined at autopsy of patients succumbing to the disease demonstrating evidence of multiple myeloma. When alive, only 12% of these same patients demonstrated otologic symptoms (181). Although the temporal bone is commonly involved in the terminal stages of the disease, symptoms related to temporal bone involvement are often outweighed by the overwhelming skeletal disease (182). Treatment regimens include radiation therapy, bisphosphonates, and stem-cell transplants.

See Chapter 17 for further discussion of this topic.

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment