Neurologic Manifestations of Systemic Disease: Disturbances of the Kidneys, Electrolytes, Water Balance, Rheumatology, Hematology/Oncology, Alcohol, and Iatrogenic ConditionsKevin M. Biglan
NEUROLOGIC COMPLICATIONS OF RENAL DISEASE
Acute and chronic renal failure has a variety of deleterious effects on the nervous system. The mechanism of these effects is multifactorial and is due to a combination of uremia, disturbances of electrolytes and water balance, impaired drug metabolism, anemia, associated comorbid illness, and the effects of hemodialysis. The incidence of chronic renal failure increases with increasing age (12), and uremia accounts for 10% of delirium in the elderly (134).
ACUTE COMPLICATIONS OF RENAL FAILURE
Uremic Encephalopathy
Encephalopathy is common in acute renal failure. Given the increased risk of delirium in the elderly (67), encephalopathy is nearly universal in the older patient who develops an acute deterioration in renal function. Uremic encephalopathy is clinically similar to delirium from other metabolic derangements (179,180). Table 29-10 summarizes the clinical manifestations of this condition (30,179,180), with fatigue, apathy, difficulty with attention and concentration, and subtle motor signs predominating early. Later in the course, uremic encephalopathy can progress to coma and seizures (30,179,180). Symmetric upper motor neuron signs may also be seen.
The level of uremia correlates poorly with the degree of impairment, with the rapidity of renal deterioration being more important in the development of encephalopathy (30). Encephalopathy can occur not only in acute renal failure but also in the setting of decompensated chronic renal failure. Chronic renal failure can also predispose patients to delirium from other causes (67).
Table 29-10. Manifestations of Uremic Encephalopathy | |||||||
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Computed tomography (CT) and magnetic resonance imaging (MRI) can reveal nonspecific changes but should be performed in all patients receiving hemodialysis secondary to the risk of spontaneous subdural hematomas (SDHs) (see Complications of Dialysis). Electroencephalography (EEG) can be useful in determining whether superimposed seizures are a contributing factor to a patient’s confusion. In the absence of seizures, the EEG will show generalized slowing (30,179,180); however, spike and wave complexes can be seen in up to 14% of patients without clinical seizure activity (30).
Treatment of uremic encephalopathy entails correcting the underlying renal disease and, possibly, hemodialysis. Correction of an underlying anemia can further improve cognitive function in some patients (173). Seizures should be treated appropriately. Caution must be used with certain anticonvulsants (i.e., phenytoin and valproic acid) (11) because of reduced protein binding in renal failure secondary to hypoalbuminemia and a resultant increase in free levels of these drugs (179,180).
CHRONIC COMPLICATIONS OF RENAL FAILURE
Uremic Neuropathy
Neuropathy occurs in 60% to 100% of patients with chronic renal failure on hemodialysis (123). It is more common in older patients and men (30). It is a distal, symmetric, sensorimotor axonal polyneuropathy predominantly involving large fibers (30,123,180). Clinically, patients complain of paresthesias and distal motor weakness. Findings on physical examination are diminished or absent reflexes, muscle atrophy, and a stocking-glove sensory loss.
The severity and course are variable. Although mild cases may resolve or improve with dialysis, most cases are not appreciably influenced by dialysis (123). Successful renal transplantation is the only known cure and results in a dramatic improvement within days of transplantation (123).
Restless legs syndrome, a frequent accompaniment (212), is a condition characterized by abnormal sensations in the legs and arms accompanied by a desire to move the legs. Standing or walking relieves the symptoms, whereas rest exacerbates them. The symptoms are more severe in the evening or at night (221). Dopamine agonists (i.e., pramipexole or ropinirole) (165,212), given at night, are useful for ameliorating the symptoms.
Myopathy
Myopathy in renal failure is multifactorial secondary to cachexia, steroids, and water and electrolyte disturbances (74). Proximal muscle weakness and associated atrophy make up the clinical picture. Rarely, a fulminant painful myopathy associated with necrosis occurs (30). Neurophysiologic studies reveal a myopathic pattern, whereas muscle histology is nonspecific.
Cerebrovascular Disease
Cerebrovascular disease is a major cause of morbidity and mortality in patients with chronic renal failure, with a nearly 20% prevalence rate in one large series of chronic hemodialysis patients (41). Although this higher risk is likely associated with shared risk factors such as diabetes mellitus, hypertension, dyslipidemia, and smoking, chronic renal failure itself has been independently associated with an increased risk of stroke (1). As in the general population, increasing age is an important risk factor for stroke in this population. In addition, patients with chronic renal failure are at a higher risk for hemorrhagic stroke due to platelet dysfunction associated with uremia (53).
In general, the evaluation and management of stroke in patients with renal failure are the same as in other patients with stroke. Modifiable risk factors should be addressed in an attempt to prevent future strokes. Angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers are recommended in diabetic kidney disease or nondiabetic kidney disease with significant proteinuria (210). Some controversy exists regarding the benefit of statins on stroke prevention in this population, however, and pending future statin studies are currently recommended (19). Anemia appears to be an important independent risk factor for stroke in renal failure, and erythropoietin injections may be considered as a preventive measure (1).
COMPLICATIONS OF DIALYSIS
Dialysis Disequilibrium Syndrome
The elderly are at high risk for developing dialysis disequilibrium syndrome, a rare but life-threatening complication of peritoneal dialysis or hemodialysis. Dialysis disequilibrium syndrome was more common prior to 1970 when patients were dialyzed more rapidly (30,179,180).
A wide variety of symptoms may be seen, from the mild (headaches, myalgias, and restlessness) to the severe (coma and seizures). Symptoms begin at the end of dialysis or shortly thereafter. Dialysis disequilibrium syndrome is the result of large osmotic gradients between the brain and plasma, resulting in large fluid shifts into the brain parenchyma (201). Clinically, this results in increased intracranial pressure and obtundation from cerebral edema (30,179,180).
Prevention is the key to managing this problem. Slow dialysis, every 1 to 2 days, and the use of osmotically active solutes have reduced the frequency of this complication.
Dementia
Impaired cognition is common in end-stage renal disease (129). A significantly higher percentage of patients on dialysis will have dementia compared with age-matched controls, with an annual incidence of 4.2% in elderly patients on dialysis (73,129). Although the cause is unclear, ischemic disease appears to play a prominent role (73,129). Also, cerebral atrophy is seen in patients with renal failure on dialysis, and the degree of atrophy correlates with duration of dialysis (118).
In addition, a specific syndrome of a progressive dementia has been associated with chronically dialyzed patients. It is commonly referred to as dialysis dementia, dialysis encephalopathy, or progressive myoclonic dialysis encephalopathy (162). Dialysis dementia is a progressive and potentially fatal disorder characterized by progressive cognitive decline (30). Disorders of speech—a slowness and hesitancy of speech and paraphasia—occur commonly and early in the course of this disorder (30,162). Some cases progress to an overt expressive aphasia, whereas others may represent an apraxia of speech (162). Myoclonus is ubiquitous, and ataxia and apraxia can occur. Changes in personality, with psychosis and hallucinations, occur in more
advanced cases. Seizures occur late in as many as 60% to 100% of patients (30,162).
advanced cases. Seizures occur late in as many as 60% to 100% of patients (30,162).
Frontal intermittent rhythmic delta activity is the most characteristic finding on EEG (30,162). Generalized slowing, triphasic waves, and spike and wave activity may also be seen on EEG (162). Neuroimaging and cerebrospinal fluid (CSF) examination are useful in ruling out other causes of the patient’s deterioration (30).
Dialysis dementia has been linked to aluminum concentrations in dialysate water supply (48,136). The use of deionized water with low aluminum levels has nearly eliminated this condition (48). However, sporadic cases do occur and may be associated with aluminum-containing, phosphate-binding agents used in this population (30). Treatment consists of the use of aluminum-free water in the dialysate and aluminum chelating agents (desferrioxamine). Paradoxically, a period of clinical worsening may occur at the initiation of chelation therapy (30,102).
Subdural Hematoma
SDH can occur in 1% to 3% of patients receiving hemodialysis in the absence of trauma (30). The cause is multifactorial and likely reflects a combination of cerebral atrophy, large fluid shifts during dialysis, coagulopathies, and the use of anticoagulants during dialysis. Signs and symptoms include diminished level of consciousness, headache, and focal neurologic deficits. However, bilateral SDHs are common and can present with confusion, lethargy, and gait dysfunction. Therefore, a high index of suspicion must be maintained for this complication. All patients on dialysis who develop an alteration in mental status should have a CT scan to rule out the possibility of SDH. Conservative treatment, with close clinical follow-up, may be all that is needed in some patients; however, neurosurgical intervention may also be required.
NEUROLOGIC COMPLICATIONS OF DISTURBANCES OF ELECTROLYTES AND WATER BALANCE
DISTURBANCES OF SODIUM AND WATER BALANCE
Dehydration
Dehydration is the most common fluid disturbance in the elderly (132). Dehydration accounts for 1.5% of hospital admissions of the elderly and frequently complicates other illnesses (182). In addition, dehydration is a major risk factor for the development of delirium in the inpatient setting (109). Table 29-11 summarizes the major risk factors for dehydration in elderly nursing home patients (132).
Table 29-11. Risk Factors for Dehydration | ||||||
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Treatment of dehydration requires removing any offending drugs and hydration with isotonic saline until the patient is hemodynamically stable. Subsequently, 0.45% saline solution can be used until the water deficit is corrected. Caution must be used in using hypotonic solutions as they may precipitate hyponatremia.
Hyponatremia
In general, water balance is strictly maintained such that the serum sodium concentrations range between 138 and 142 mmol/L (125). Deficits in the ability of the kidney to dilute the urine, coupled with increased fluid intake, results in hyponatremia.
Neurologic complications of hyponatremia are dependent on the severity of the hyponatremia and the rate that it evolved and range from delirium to coma and seizures from cerebral edema (52,125). The decision to treat hyponatremia should be based on the presence of symptoms, severity and duration of hyponatremia, and the presence of hypovolemia (34).
When hyponatremia is known to have developed in <48 hours and the patient has neurologic symptoms, then rapid correction is warranted (125). This can be achieved by the infusion of hypertonic saline (3% NaCl) in combination with a loop diuretic (125). When the duration of hyponatremia is >48 hours or unknown and the patient has symptoms, it must be corrected with extreme caution to avoid central pontine myelinolysis (CPM) (125,131). The rate of sodium replacement should not exceed 1 to 2 mEq/L/h and not exceed 12 mEq/L in the first 24 hours or 18 mEq/L in the first 48 hours of treatment (206). Frequent monitoring of clinical and electrolyte status is needed in all patients undergoing treatment regardless of the rate of correction. Acute treatment should end when the patient’s symptoms resolve, a serum sodium of 120 mEq/L is reached, or an increase of 20 mEq/L occurs. In patients with chronic hyponatremia and minimal or no neurologic symptoms, immediate treatment is not warranted, and conservative therapies such as fluid restriction can be instituted (217).
Hypernatremia
Hypernatremia is less common than hyponatremia; however, central nervous system (CNS) manifestations are frequently more prominent (125). Also, the elderly are more susceptible to hypernatremia than other age
groups due to dehydration (18). Symptoms of delirium, with alterations in level of consciousness and seizures, can occur (52,125). Focal deficits may reflect subdural hemorrhage if the change in sodium levels occurred rapidly (10). In the most common setting, hypernatremia reflects a hypovolemic state, and treatment is as outlined for dehydration.
groups due to dehydration (18). Symptoms of delirium, with alterations in level of consciousness and seizures, can occur (52,125). Focal deficits may reflect subdural hemorrhage if the change in sodium levels occurred rapidly (10). In the most common setting, hypernatremia reflects a hypovolemic state, and treatment is as outlined for dehydration.
Central Pontine Myelinolysis
CPM is a catastrophic disorder associated with the rapid correction of hyponatremia. The term CPM is misleading because extrapontine white matter is frequently involved. Pathologically, extensive and symmetric white matter dysmyelination is out of proportion to neuronal loss. Clinical presentations vary, depending on the degree and location of myelinolysis, although more than 90% of patients will have the classic findings of spastic quadriparesis and pseudobulbar palsy. Prognosis varies from death to complete recovery. MRI of the brain reveals symmetric areas of T2 hyperintensity in the pontine and extrapontine white matter. Caution must be used in interpreting scans too early because the characteristic changes may delay the clinical presentation of CPM by 2 weeks (39,131).
The only treatment is prevention, and the hyponatremia must be corrected cautiously. However, CPM has been reported to develop despite safe correction of hyponatremia (131). Therefore, correcting the hyponatremia with the associated potential of myelinolysis must outweigh the risks of illness from hyponatremia.
DISTURBANCES OF POTASSIUM BALANCE
Hypokalemia
Hypokalemia is common in elderly patients admitted to the hospital (116). In its mildest forms, it is associated with myalgias and proximal muscle weakness; in severe cases, profound weakness, rhabdomyolysis, and tetany can occur (10). Rarely, this will occur acutely and be associated with thyrotoxicosis (3,216). Potassium replacement is effective in treating the symptoms (10).
Hyperkalemia
Hyperkalemia causes a profound, rapidly progressive, flaccid quadriplegia sparing the cranial nerve musculature (10,61). Paresthesias are sometimes seen. Drugs or renal failure are common causes (61). Mortality is related to cardiovascular complications (10). Aggressive reduction of the serum potassium results in resolution of the symptoms (61).
DISTURBANCES OF CALCIUM BALANCE
Hypocalcemia
Hypocalcemia is an abnormally low concentration of ionized calcium. It is usually the result of hypoparathyroidism (64,65) and is a well-recognized complication of thyroid or parathyroid surgery (10). Tetany associated with perioral and limb paresthesia is the most common manifestation (10,65). Seizures and psychosis can also occur (10,52). The Chvostek sign (i.e., spasm of the facial muscles with percussion of the facial nerve) and Trousseau sign (i.e., spasm of the hand after inflation of a blood pressure cuff above the systolic blood pressure) are positive (64,65). Symptoms correct with calcium replacement (10).
Hypercalcemia
Hypercalcemia, which is more common than hypocalcemia, may be the result of hyperparathyroidism, malignancy, or drugs (64,65,95). Delirium can occur, but seizures are rare. Muscle weakness and fatigability are peripheral manifestations (10). Therapy is based on the underlying cause and clinical symptoms (95). Intravenous hydration, loop diuretics, glucocorticoids, and calcitonin can be used nonspecifically to reduce serum calcium levels while the underlying cause is being investigated (64,65).
DISTURBANCES OF MAGNESIUM BALANCE
Hypomagnesemia
Hypomagnesemia results from poor dietary intake or absorption or through increased magnesium loss via renal mechanisms (25). It is frequently associated with hypocalcemia, and the clinical symptoms are similar (10,25). Hypomagnesemia must always be suspected when a patient with hypocalcemia fails to respond to calcium replacement (10). Treatment with oral magnesium supplementation is usually sufficient.
Hypermagnesemia
Hypermagnesemia is rarely relevant clinically and is usually associated with renal failure (64,65). Somnolence, confusion, and weakness associated with reduced or absent reflexes are the neurologic manifestations (10). Treatment consists of dialysis in renal failure or intravenous administration of 100 to 200 mg of calcium (64,65).
NEUROLOGIC COMPLICATIONS OF CANCER
The incidence of cancer increases with age, putting the elderly at an increased risk for developing neurologic complications from cancer and its treatment. Besides routine chemotherapy, neurologic symptoms are the most common reason for hospitalization of individuals with known cancer (81). Neurologic disease in cancer occurs via four separate mechanisms: (a) metastatic involvement of brain parenchyma, meninges, or spinal cord; (b) direct extension into neural structures
(e.g., lumbosacral plexus); (c) remote involvement (i.e., paraneoplastic syndromes); and (d) neurotoxic effects of cancer therapy (44,81,82,111). This section briefly discusses the first three mechanisms (see Chapter 28 for additional information on these topics), focusing primarily on the toxic effects of cancer therapy.
(e.g., lumbosacral plexus); (c) remote involvement (i.e., paraneoplastic syndromes); and (d) neurotoxic effects of cancer therapy (44,81,82,111). This section briefly discusses the first three mechanisms (see Chapter 28 for additional information on these topics), focusing primarily on the toxic effects of cancer therapy.
METASTATIC DISEASE
Metastasis can occur in any portion of the nervous system, although the brain is the most common region involved (44). Spinal cord involvement occurs through vertebral body metastasis and subsequent extension into the epidural space with cord compression (44). Less commonly, metastasis to the meninges can occur, presenting with symptoms of increased intracranial pressure, multiple cranial neuropathies, and multiple radiculopathies (44,87). Leptomeningeal metastases have a poor prognosis without aggressive therapy (87). Lung and breast cancers are the most common tumors to metastasize to the nervous system (44,87).
DIRECT INVASION
Pancoast tumors of the lung may extend into the brachial plexus, causing plexopathies that affect the muscles of the lower cord of the brachial plexus and Horner syndrome (115). Pelvic tumors can extend into the lumbosacral plexus (111,172). Finally, tumors of the nasopharynx can invade through the skull base, causing cranial neuropathies, pneumocephalus, and death (121,171). Treatment is dependent on tumor type and location.
Table 29-12. Antineuronal Antibody and Associated Paraneoplastic Neurologic Syndromes | |||||||||||||||||||||||||||||||||
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PARANEOPLASTIC SYNDROMES
Neurologic paraneoplastic syndromes refer to signs and symptoms affecting nervous system tissue remote to the primary cancer and its metastases. Although these syndromes are common in specific cancers (e.g., myasthenia gravis and thymoma), they affect <1% of all cancer patients. However, they do have a significant impact on the patient’s quality of life and can precede the cancer diagnosis in 50% of cases (155). Table 29-12 summarizes the well-characterized paraneoplastic syndromes and their associated antineuronal antibodies (46,155,175,185). The combination of CT scan and fluorodeoxyglucose (FDG) positron emission tomography (PET) is 100% sensitive at detecting tumors in patients with antineuronal antibodies and a paraneoplastic syndrome (133).
COMPLICATIONS OF CANCER TREATMENT
Chemotherapeutic Agents
Neurologic side effects of cancer treatments are common and frequently add to the confusion surrounding neurologic symptoms in these patients. Many chemotherapeutic agents have neurotoxic side effects (119).
Methotrexate
Intrathecal methotrexate (MTX) causes an acute meningeal reaction approximately 2 to 4 hours after administration. Meningismus, headache, nausea, lethargy, and spinal fluid pleocytosis are common (119). No long-term sequelae of this manifestation occur, and it resolves spontaneously in days (82,119). However, it may easily be confused with bacterial meningitis, which may result in delaying treatment.
A subacute reaction to MTX can occur after multiple intrathecal injections (82). This reaction results in clinical signs of a spinal cord lesion with paraplegia and sensory level and bladder dysfunction. The condition gradually improves over days to months, and recovery is variable (119).
Encephalopathies associated with long-term MTX use have been identified independent of the method of delivery. Patients are confused, lethargic, and ataxic and may have seizures. A delayed leukoencephalopathy may also be seen months to years after treatment with intrathecal or intravenous MTX (68,82,119). This condition begins insidiously and progresses to dementia. It is much more common in older patients who also received whole-brain radiation (77).
Cytarabine
Cytarabine (AraC) can cause a reversible cerebellar syndrome peaking after 2 to 3 days of onset. Most patients recover completely after cessation of the drug. Age >50 years appears to be the greatest risk factor for this complication (176). AraC given intrathecally can cause a chemical meningitis and myelopathy similar to that seen with MTX (119).
Platinum
Platinum-based drugs (cisplatin and oxaliplatin) have long been associated with ototoxicity, causing symptoms of tinnitus and hearing loss (82,119). A distal symmetric, predominantly sensory axonal neuropathy is also seen (82,119). The neuropathy is dose dependent, and synergistic toxicity is seen with doxorubicin, vindesine, and etoposide (190). In addition, oxaliplatin causes an acute sensory neuropathy characterized by cold sensitivity, paresthesia, and pseudolaryngospasm that is rapidly reversible (88).
Vinca Alkaloids
The use of vinca alkaloids is limited due to their common neurotoxicities (82,119). Peripheral neuropathy occurs early in nearly all patients receiving vinca alkaloids (e.g., vincristine) (15,82,119). The neuropathy is a distal symmetric sensorimotor axonal polyneuropathy. Motor manifestations resolve with discontinuation of the drug, but sensory manifestations persist (82). Vincristine has been associated with an autonomic neuropathy that preferentially affects the gastrointestinal tract, causing constipation. Cranial neuropathies are also seen and must be distinguished from carcinomatous involvement of the meninges (82,119).
Hexamethylmelamine
Fluorouracil
Fluorouracil can cause an acute cerebellar syndrome 2 weeks to 6 months into treatment (82,119). The incidence of this complication appears to be dose related (119). This syndrome is reversible with discontinuation of the drug; however, it rapidly recurs if the drug is reintroduced (82,119). Metastasis to the cerebellum constitutes the major differential diagnosis and must be ruled out if this condition occurs.
The combination of fluorouracil with levamisole has been associated with a multifocal inflammatory leukoencephalopathy. Symptoms begin within a few months of initiating treatment and are characterized by confusion and focal neurologic signs. MRI reveals multiple gadolinium-enhancing white matter lesions. Discontinuation of the drug and treatment with corticosteroids may result in improvement (176).
Taxanes
The taxanes (e.g., docetaxel and paclitaxel) are effective treatments against metastatic breast cancers, early breast cancer, and treatment-resistant ovarian cancers. The taxanes cause a distal, predominantly sensory axonal neuropathy (191).
RADIATION THERAPY
Radiation can have a negative impact on the nervous system by direct toxic effects of radiation on neural tissues or by damaging the vasculature that supplies neural tissue (49,57,153,169,187). Radiation-induced injury to the nervous system occurs when the neural tissue lies within the field of radiation. This can occur as incidental radiation (radiation to head and neck tumors with incidental brain radiation) or directly (whole-brain radiation for metastatic tumors).
Spinal Cord Injury
A transient myelopathy associated with incidental radiation to the spinal cord is the most common spinal cord complication of radiation treatments (57). Mild symptoms consisting of paresthesia and Lhermitte sign develop several months after treatment. Neurologic examination is usually unremarkable, and the symptoms resolve over 1 to 9 months (57).
A delayed progressive myelopathy is a more feared complication of radiation involving the spinal cord. The symptoms can occur as early as a few months after treatment or as long as 5 years after treatment (57). Paresthesia and anesthesia are the earliest manifestations, followed by disabling weakness and bladder dysfunction with the spinal cord level involved corresponding with the level radiated. A Brown-Sequard hemi-cord pattern may be seen (57,169). Neuroimaging is necessary to distinguish this condition from metastatic disease causing a compressive myelopathy.
An isolated lower motor neuron syndrome has been reported in individuals who have received spinal radiation. The lumbosacral spine is preferentially involved in this condition (209).
Cerebral Injury
Cerebral injury following therapeutic radiation is classified by the time of onset following treatment: acute, early delayed, and late. An acute reaction to brain radiation occurs within days of radiotherapy and manifests with headache, lethargy, and nausea. Prophylactic dexamethasone is recommended for individuals with a large tumor burden or who are receiving a large dose of radiation (57).
Early delayed encephalopathy is a self-limited complication occurring a few months after radiation and lasting several weeks before resolving (57). Headache and lethargy are the prominent symptoms. Neuroimaging may show worsening edema and be difficult to distinguish from tumor recurrence. Stereotactic biopsy may be necessary to rule out treatment failures. Dexamethasone may be beneficial.
Late cerebral injury is irreversible and can occur months to years after brain radiation (57). Dementia, seizures, headache, personality changes, and focal neurologic signs are common (49,57,187). Imaging may reveal focal abnormalities indistinguishable from tumor or diffuse abnormalities in the deep white matter and cerebral atrophy (49,57). DeAngelis et al. (49) recommend a trial of steroids and consideration of ventriculoperitoneal shunting.
Cerebrovascular disease of the intracranial and extracranial vessels is another cause of delayed cerebral injury associated with exposure of these vessels to therapeutic radiation. Transient ischemic attacks and strokes may develop secondary to radiation-induced accelerated atherosclerosis (57,153).
Peripheral Injury
Peripheral effects of radiation mainly include plexopathies associated with radiation of these structures (98). This condition may be difficult to distinguish from direct invasion of the plexus with tumor. Clinical and electrophysiologic myokymia may be more common in radiation injury than plexopathy from other causes (98). MRI of the plexus may be useful in identifying the cause.
NEUROLOGIC COMPLICATIONS OF HEMATOLOGIC ILLNESS
THROMBOTIC THROMBOCYTOPENIC PURPURA
Thrombotic thrombocytopenic purpura is a severe multisystem disease characterized by fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and impaired renal function (60). It tends to affect a younger population but can be seen in any age group. Table 29-13 reviews conditions affecting the elderly where thrombotic thrombocytopenic purpura is seen (60,80).
Table 29-13. Differential Diagnosis of Thrombotic Thrombocytopenic Purpura in the Elderly | ||||||
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Neurologic complications can be secondary to ischemia in the small blood vessels or hemorrhage, resulting in permanent neurologic deficits. Transient and fluctuating neurologic signs without permanent deficits are more common. These can include headache, delirium, motor and sensory deficits, seizures, and even coma (60).
DISSEMINATED INTRAVASCULAR COAGULATION
Disseminated intravascular coagulation (DIC) is a syndrome of widespread intravascular thrombosis followed by thrombocytopenia and hemorrhage. Multiple causes exist for DIC, including infection, trauma, cancer, and vascular diseases. Treatment is geared toward the underlying cause. Additionally, supportive care is frequently necessary. Fluid resuscitation, fresh frozen plasma, and platelet transfusions are useful. The neurologic complications are related to CNS ischemia (stroke) and hemorrhage (72).
NEUROLOGIC MANIFESTATIONS OF RHEUMATOLOGIC DISEASE AND SYSTEMIC VASCULITIDES
EPIDEMIOLOGY OF RHEUMATIC DISEASE IN THE ELDERLY
Spinal osteoarthritis and spondylosis are nearly universal consequences of aging. Other rheumatologic diseases are less common. Although most autoimmune
rheumatologic diseases begin in young to middle adulthood, they can also affect the older adult population. Notable exceptions include rheumatoid arthritis and giant cell arteritis, which increase in prevalence with age (186). This section will focus on the rheumatologic disorders primarily affecting the elderly. Table 29-14 provides information on the epidemiology of these disorders (17,33,56,100,113,126,154,163,181,186,195,199,204).
rheumatologic diseases begin in young to middle adulthood, they can also affect the older adult population. Notable exceptions include rheumatoid arthritis and giant cell arteritis, which increase in prevalence with age (186). This section will focus on the rheumatologic disorders primarily affecting the elderly. Table 29-14 provides information on the epidemiology of these disorders (17,33,56,100,113,126,154,163,181,186,195,199,204).
The incidence of neurologic complications of rheumatologic diseases varies from the exceedingly rare (e.g., the sensory neuronopathy of Sjögren’s disease) (69,186) to the very common (e.g., headache in giant cell arteritis) (32). However, these neurologic complications may be the initial manifestation of the disease (90) and are frequently associated with high morbidity and mortality. For these reasons, this subgroup of disorders deserves special attention.
OSTEOARTHRITIS
Osteoarthritis is ubiquitous in the elderly and is a common cause of neurologic disease and disability. The most common complaint associated with osteoarthritis is pain. Low back pain is one of the most common reasons patients seek medical attention (186). Frank neurologic dysfunction secondary to radiculopathy, mononeuropathy, and myelopathy are common consequences of degenerative disease of the joints. Infrequently, osteoarthritis can impair cerebral blood flow, producing symptoms of cerebral ischemia (79).
Osteoarthritis is characterized by the slow, steady progression of articular pain. The pain worsens with use, is relieved with rest, and has little associated morning stiffness. Physical examination reveals a painful enlarged joint with a limited range of motion. Peripheral osteoarthropathy is rarely a cause of neurologic dysfunction. However, entrapment neuropathy at the carpal tunnel may be related to osteophyte formation and bony hypertrophy (55).
Table 29-14. Epidemiology of Rheumatic Diseases | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Osteoarthritis of the spine associated with spondylosis of the intervertebral disks is a much more common cause of neurologic morbidity. Spondylosis refers to the desiccation and degeneration of the intervertebral disk associated with aging or the combination of osteoarthritis of the intervertebral joints and degeneration of the intervertebral disks (186,213). The two conditions invariably coexist, and disk desiccation and loss of disk height associated with aging are likely causative factors in osteoarthritis of intervertebral joints (178).
Radiculopathy
Radiculopathies can result from two different mechanisms. Encroachment of the neural foramina by osteophytes and bony spurs is the most common cause of radiculopathy in the elderly. The foraminal narrowing usually remains quiescent until a minor trauma results in symptoms (213). Less common in the older population is acute disk herniation with resultant foraminal narrowing.
Clinically, radiculopathy is characterized by pain with radiation in a radicular pattern. Weakness and numbness in the distribution of the nerve root involved can also occur. Excessive mobility of the neck or back will exacerbate the symptoms, as will Valsalva maneuvers (213). In the cervical spine, the C6-7 followed by the C5-6 disk space is most commonly involved. In the lumbosacral spine the L4-5 and L5-S1 disks are usually involved (186). Table 29-15 outlines the clinical symptoms seen with radiculopathy by the nerve root involved (28,186).
Table 29-15. Signs and Symptoms of Radiculopathy by Disk Level Affected | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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A variety of examination maneuvers are useful in making the diagnosis of radiculopathy. In the Spurling maneuver, the head is extended and rotated toward the symptomatic side, resulting in reproduction of the radicular symptoms. The compression test entails pushing down on the head with resultant foraminal narrowing and exacerbation of symptoms. Abduction of the arm on the affected side results in pain diminishment in cervical radiculopathy (47). Lumbar radiculopathy can be similarly elicited. The straight leg-raising sign is positive if the patient reports pain radiating down the posterior aspect of the leg into the calf or foot when the hip is flexed >20 degrees while the knee is maintained in extension. A positive crossed straight leg-raising maneuver is more specific for radiculopathy but less sensitive. In this maneuver, pain is elicited in the opposite leg from the one raised (186).
Electrodiagnostic studies are useful in confirming suspected radiculopathy and in differentiating the role of other coexistent conditions (227). Plain radiographs of the cervical spine have a high false-positive rate in the elderly, frequently showing degenerative findings in asymptomatic individuals, and are not recommended in this population (150,213). Myelograms, CT scans, or MRIs readily show the anatomic relationship of the spinal roots, intravertebral disks, and neural foramina. Each study has similar sensitivity and specificity (128), although MRI better reveals nerve root and cord compression (124). In addition, MRI can rule out more serious causes of radiculopathy in the elderly (e.g., metastatic cancer and epidural infections).
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